Even though Sam was born to be Lucifer's vessel, Lucifer needed to take some precautions. So he had Azazel create the special children, in addition to freeing Lilith.
Azazel managed to open a gate to Hell, and Lilith was set free. The next step was to get Dean to Hell, so he could break the first seal. Once the first seal was broken, Lilith began breaking the rest of the 66 seals so Lucifer himself could rise. Sam was the one who broke the final seal, thus setting Lucifer free.
- Lucifer: I will never lie to you. I'll never trick you. But you will let me in.
- Sam: Why me?
- Lucifer: Because it had to be you. It always had to be you.
- - Free To Be You and Me.
Lucifer came to Sam in Free To Be You and Me disguised as Jessica Moore to try to get Sam to change. He eventually reveals himself as Lucifer, which shocks Sam. Lucifer tells Sam that he is Lucifer's true vessel, confidently adding that Sam will say "yes", despite Sam's insistence that he won't. Now knowing his destiny, Sam decides to join up with Dean again to prevent it.
To avoid his fate, Sam joins in the search for the colt, hoping it will kill Lucifer. In Abandon All Hope..., Sam uses himself as bait to draw Lucifer's attention so Dean can sneak up and shoot him. Although fired at point-blank range, Lucifer survives and continues with his ritual of summoning Death. Meanwhile, he tells Sam that in about six months, he is going to consent to possession. Lucifer follows this statement with a story about him and Michael, and comments on how it's similar to Sam's own life. Sam manages to escape from Lucifer with the help of Castiel.
They briefly meet again in Hammer of the Gods, when Lucifer arrives at the motel Sam and Dean are trapped in by the pagan gods, who Lucifer proceeds to slaughter.
Sam forms the idea of tricking Lucifer back into the cage in The Devil You Know, by saying "yes", and jumping into it with Lucifer inside him. Bobby points out to Sam that Lucifer will poke at everything to get control, but Sam believes he can best Lucifer.
In Swan Song, Sam and Dean go to confront Lucifer in Detroit, who tells them that he knows of their plan, but is willing to give it a try, creating a wager. Sam gives consent, and Lucifer abandons his old vessel. Within minutes, Lucifer overpowers Sam and gains control over the vessel. Trying to make Sam accept it, he reveals Azazel's gang of demons that have been watching Sam since he was a child, and kills them all.
Lucifer initially spares Dean's life for Sam's sake, but when Dean becomes a major annoyance especially during the confrontation at Stull Cemetery, Lucifer attacks Dean with an inch of his life. Before he can deal the final blow, however, Sam manages to wrestle control back and open the cage, and throws himself, Lucifer, along with Adam and Michael into the cage.
Since Sam jumped into the cage, Lucifer had ruthlessly tormented Sam's soul. Sam's soul was in the cage with Michael and Lucifer for a year and a half in Earth time, tortured and abused by the latter archangel. Being an immortal soul, Sam's essence could not be broken, but was left with severe psychological damage.
- Sam: You’re not real.
- Lucifer: Right. You think this fruit-bat fever dream is reality? You come back, I'm sorry, with no soul like some peppy American Psycho, till Saint Dean glues you back together again by buying you some magic amnesia. You’re real. I’m very real. Everything between is what we call set dressing.
- Sam: No.
- Lucifer: You’re still in my cell. You’re my bunkmate, buddy. You’re my little bitch, in every sense of the term. Sam. Sam.
Since the wall in Sam's head broke, he began remembering Hell, and hallucinating. Most notably, hallucinating Lucifer. Lucifer appears to Sam in Meet the New Boss, who quickly tells himself that Lucifer isn't real. Lucifer denies this, and that Sam really never got out, and is still in the cage with him. This whole reality, is just another form of torture. Back at Bobby's, Lucifer continues to mock Sam, and Sam reveals to Dean that he is seeing Lucifer. Sam is still confused what's real because Lucifer is very convincing. Every time Sam is asked if he's fine, he sees Lucifer, and pretends he is. Sam later approaches Lucifer and asks why he doesn't just end it. Lucifer tells Sam that he has Sam right where he wants him. It will only end when Sam can't take it anymore.
Soon after, Lucifer takes on Dean's form and tricks Sam into leaving Bobby's and go to a warehouse. Inside, Lucifer changes back, and Sam pulls a gun on him. Lucifer reveals to Sam the only way to end it is for Sam to kill himself. Sam tries to shoot him but misses. Then the real Dean arrives and tries to convince Sam to ignore Lucifer's words. Dean teaches Sam how to get rid of the fake Lucifer by using the pain from the scar he acquired.
Lucifer begins to flicker. Realizing he can control this, Sam uses the pain to banish Lucifer from his sight. Lucifer returns moments later in an ambulance transporting Sam to the hospital, after he sustained a head injury from a confrontation with Edgar. Here, Lucifer admits to Sam that he isn't real but he also isn't going anywhere.
The fake Lucifer continues to bother Sam for weeks, but doesn't truly become a problem until the events of Repo Man. Lucifer tries to get Sam's attention. Sam in turn, tries to ignore him and uses his scar to get rid of Lucifer more than once. When Dean disappears during a case, Lucifer helps Sam by providing clues. They search Jeffrey's room and interrogate Nora, with Lucifer managing to convince Sam to get rough with her for information.
After they find Dean, Sam tries to banish Lucifer again, but as he welcomed Lucfier's help, as such welcomed Lucifer into his mind, his scar can no longer be used to get rid of Lucifer, causing the archangel to burst out laughing when he tried it.
Now no longer able to be banished, Lucifer begins to torment Sam causing Sam to lose sleep. Sam attempts to drink and use drugs to fall asleep, but nothing works. This leads to Sam landing in a mental ward at the hospital. Lucifer does everything from lighting fire crackers, to playing with a megaphone, in order to keep Sam awake. Sam's condition crumbles to a state where he can only see Lucifer. Thanks to Castiel's help, the hallucination of the archangel is removed from Sam's mind, and Sam quickly recovers.
- “Sam Winchester. My old roomie. Hug it out?”
Sam is visibly scared and agitated at the thought of meeting his former torturer. Lucifer greets Sam happily upon their first reunion since Death retrieved Sam's soul. The two discuss the current situation involving The Darkness, and when Lucifer requests Sam to become his vessel again in order to obtain his help, Sam ultimately declines.
The warding charms suddenly fall, and Lucifer manages to bring Sam into the cage. Sam shows clear signs of fear, but manages to stay calm, since he believes this is what God wants. When Lucifer reveals that the visions came from him, and not God, Sam sheds a tear, now horrified over his current predicament.
Lucifer reassures Sam that he won't torture him, even though he could, adding how it was "so five years ago". Lucifer instead takes Sam through memory lane, and tries to show Sam how soft he's become. Lucifer admits to having some degree of respect for Sam, since Sam stood up against him at Stull Cemetery. He doesn't however, like Sam, claiming him to be "sort of prissy".Despite Lucifer's efforts, Sam persistently refuses to become Lucifer's vessel, stating that he would rather watch his loved ones die than become Lucifer's "bitch". Lucifer thus chooses Plan B and proceeds to beat Sam up and later Castiel and Dean too, when they arrive. Team Free Will survives the encounter when Rowena apparently sends Lucifer back to his cell.
- Sam – “...Lucifer.”
- Lucifer – “In the flesh.”
- ―The Vessel.
"Castiel" laughs and slams Sam into a pillar. He expresses his glee over killing Sam since he is no longer needed and will use his soul since he was asked nicely. Sam realizes then that this is in fact Lucifer talking to him. The archangel nearly kills Sam as intended but the real Castiel regains control of his body just in time to save Sam.
Sam and Castiel agree to let Lucifer take control so he can bring Dean back. When Lucifer returns with Dean, Sam reveals the angel isn't Castiel and begins drawing a banishing sigil. Sam activates the sigil just in time to save Dean from Lucifer's wrath.
Sam meets Lucifer again a few weeks later, after setting up a trap to bind Lucifer so that he and Dean can get Castiel to expel the archangel. When this plan fails, Sam and Dean are nearly suffocated to death until Amara intervenes, saving them both, but also kidnapping their friend.
Sam later retrieves Lucifer from Amara in a rescue mission, which consists of Metatron and Donatello, as well as Dean, who serves as a distraction for Amara. Using Donatello's prophet abilities, Sam is able to arrive at the location where Lucifer is being held. Sam offers to free him if he is willing to work with them and God, to which Lucifer replies very firmly that he will, since he is not a fan of Amara.
Initially, Sam hoped Lucifer could teleport them out of the place, but the archangel reveals he can't, forcing them to go back the way they came. Amara begins closing in, having discovered something was up, so Sam hurriedly carries Lucifer out of the hideout and into the Impala, while Metatron stays behind.
They are unfortunately confronted by Amara on the road, but the trio are saved in time thanks to the intervention of God. Lucifer is also healed of his wounds by God.
While Sam and Dean take Donatello home and buy groceries, Lucifer starts having an argument with his father. When the brothers return, Lucifer is angry over God not apologizing, and nearly kills them for interrupting. He eventually storms off, and locks himself in Sam's room. Sam and Dean try to get him to come out, but Lucifer refuses to do so unless God has something to say. This leaves Sam visibly annoyed.
Sam and Dean do manage to get the two to sit and confront each other. They try to help with the conversation, but God ultimately snaps them elsewhere. Fortunately, God manages to apologize and he and his son reconcile. The four then plan their attack on Amara, and agree to use demons, witches and angels as substitutes for the remaining three archangels.
The initial attack plan proves successful, but as God is preparing to give the Mark to Sam, Amara attacks him to prevent her re-imprisonment, saying she would rather die or kill him over a million times than go back there. Lucifer tries to save his father, but Amara easily knocks him away and removes him from his vessel. Sam and Dean are eventually left with an unconscious God and Castiel.
While under torture by Toni Bevell of the British Men of Letters, Sam informs her that he won't break easily since he has suffered worse at the hands of Lucifer.
In American Nightmare, Sam finds out from Dean that Lucifer has taken possession of rock star Vince Vincente, and thanks to Rowena, he is currently at the bottom of the ocean. Sam is confused by this, not understanding why Rowena did that, though Dean doesn't know either. When he meets Magda Peterson, a psychic who is convinced she is The Devil, Sam reassures her that she isn't, and that her powers don't make her evil.
In The One You've Been Waiting For, Sam meets Ellie Grant, a young woman who discovers that she is a descendant of Adolf Hitler. Sam tries to comfort her by explaining that her fate doesn't determine who she is by talking about how fate had intended for Sam to free Lucifer from his Cage and become his vessel. Ellie thought he was joking, however.
Sam and Lucifer meet face to face once again when Sam discovers Lucifer's plot to murder Vince Vincente's fans during a concert. Sam teams up with Dean, Castiel and Crowley in an effort to stop this from happening. After Dean scares the fans off with a gun, Sam struggles against Lucifer to hold the door open but succeeds in getting everyone outside.
After Castiel and Dean fail to subdue the archangel, Lucifer greets the three of them, and asks Sam if he "enjoyed the show". Sam demands to know why Lucifer is doing this when he and God already reconciled, but Lucifer brushes off God's apology as simply his father's means of getting his help to fight the Darkness, adding that once he was no longer needed, God left him again. He tells the brothers that they too disregarded him once he was no longer needed, though neither of them feel sorry for this.
Lucifer declares his intention to break God's already broken toys and escapes his rotting vessel in search of a higher, more influential vessel. Sam is deeply upset over the death of Vince and some of Vince's fans, and tells Dean that Vince's death has upset a lot of people. Sam blames this loss on the two of them.
In LOTUS, Lucifer is amused when Sam appears to fight him again stating "we've done this dance before." However, Lucifer takes Sam seriously when he begins using a hyperbolic pulse generator to exorcise Lucifer from Jefferson Rooney. Lucifer is helpless to stop him due to Sam's use of a sigil to significantly weaken his powers. Enraged, Lucifer tells Sam that it isn't over but Sam just responds "go to Hell", no longer threatened by Lucifer. Sam is able to exorcise Lucifer from Rooney, allowing Rowena to trap Lucifer in his Cage once more.
Unfortunately for Sam, Lucifer is not in the Cage as he had wanted, though believing he is, Sam views Lucifer's unborn child as the last trace of the archangel.
In Who We Are during a raid on the British Men of Letters compound, Sam and the American hunters manage to corner Doctor Hess. In order to convince Sam to spare her life, Doctor Hess shows Sam a file containing photos of Lucifer, proving he has escaped confinement. She reveals that Crowley is the reason, adding that Crowley is also dead because of it. Although Sam accepts the file, he doesn't want Doctor Hess' help. Sheriff Jody Mills does the job of killing Doctor Hess.
In All Along the Watchtower, Sam shows the file to Dean and Mary. He recognizes Lucifer's old vessel and knows that Lucifer is going after his son. When Sam calls Rowena for help, he gets Lucifer instead and Lucifer utterly dismisses the Winchesters as a threat. Also, due to Crowley's improvements on his vessel, he states he has no need for his "Sam suit" anymore. Crowley, who is in fact alive, arrives at the bunker to offer help. They manage to locate Kelly Kline's hideout and find Castiel still guarding her. While Sam and Dean voice their opinion that Lucifer's son must be killed, they realize that Kelly has just gone into labor.
Moments later, Lucifer arrives. Sam and Dean decide to lure Lucifer into a rift connecting their world to another universe. The rift was caused by the Nephilim being born. Sam and Dean enter the rift with Lucifer curiously following behind. Lucifer greets Sam upon seeing him, but gets distracted by Dean while Sam helps Crowleyprepare the spell that will seal the rift for good.
The spell fails to fulfill its purpose as Lucifer escapes just in time and even stabs Castiel to death right before Sam and Dean's eyes. However, Mary intervenes, and she and Lucifer tumble back into the rift, which closes on them. Sam is horrified by the loss of his mother, and is left to face Lucifer's son, who is now born.
Sam is initially frightened of Lucifer's newborn son Jack, but comes to learn that Jack is an innocent person who views Castiel as his father and has no intention of hurting anyone. Like Dean, Sam becomes delighted when Jack chooses them over his biological father, Lucifer.
Sam is informed by Dean that Lucifer likely killed their mother, but Jack later reveals that Mary is still alive in the alternate reality.
Later on, Sam learns from Rowena that she had seen Lucifer's true face moments before she was killed by him. Sam admits to having seen it before himself and the memory of it keeps him up at night. When Rowena asks how he copes, Sam further admits that he doesn't and simply pushes the thoughts down.
Sam tells Dean that if Rowena ever meets Lucifer again, he hopes she will make him suffer.
After reuniting with Castiel, Sam and Dean go on a hunt for Lucifer. While Dean and Castiel are talking with potential witnesses, Sam approaches a homeless man and shows him a photo of Lucifer. The homeless admits to knowing Lucifer and Sam's discussion with him leads the trio closer to where Lucifer is. They eventually find Lucifer in the company of Sister Jo, who agrees to help them.
When Sam, Dean and Castiel finally confront Lucifer, the archangel makes a comment about Sam's hair and claims Sam uses put-in conditioner to keep it shiny. Dean interrupts by threatening to handcuff the weakened archangel. However, Sister Jo - who is in fact Anael - double-crosses them by flinging Sam into a nearby wall. She and Lucifer ultimately escape the scene.
In "The End", Sam finally says Yes to Lucifer, and Lucifer takes over Sam's body. Soon after, Lucifer and his army of demons spread the Croatoan virus and begin wiping all of humanity. He is dressed in all white.
Oftentimes romantic things are thought by fans of this ship to have happened in the Cage, and this is the reason why Sam was having bad dreams after the wall went down.
- Fans refer to Lucifer while possessing Sam as "Samifer", a name which is also used to refer to fan works that present these two in a romantic and/or sexual relationship.
- Though Lucifer was eager for Sam to be his vessel in season 5 and was not cruel to him, when he returns in season 11, Lucifer shows no regard for Sam beyond that of a potential resource after Sam refuses to let Lucifer possess him again. Indeed, Lucifer shows no hesitation in attempting to kill Sam in The Vessel and episodes following that.
- In the same way Michael and Dean mirror each other, Lucifer and Sam are rather similar in terms of past experiences and their relationship with their fathers. The main differences are that Lucifer was abandoned by his older brother and he chose to be bitter about it. Sam was not abandoned by Dean and Sam is also more forgiving towards others.
- Ironically, when Lucifer does forgive God for his actions, God gives him another reason to hate him by abandoning him again.