Damon has decided to leave town, but through the early episodes of Season 4 seems to be looking for reasons to stay. Meredith Fell seems to be one who convinces him in ' The Rager' to stay to help Elena with her transition to Vampire. Indeed, a renewed conflict over ideology and what sort of Vampire Elena will become drives, Damon and Stefan, apart.

In The Sacrifice, Stefan and Damon visit Katherine together, as the moonstone is in the tomb with her. They come directly to Elena's home afterwards, explaining that she wanted out of the tomb, if they wanted the moonstone. They also tell her that they must "release" the spell from the moonstone so Klaus won't be able to sacrifice Elena. When Elena tells them that she doesn't want Klaus to kill everyone she cares about, both brothers express extreme surprise. Damon appears later during their meeting with Bonnie, where Jeremy tries to convince them to let him retrieve the moonstone. While he's planning to incapacitate Katherine to get the stone, Damon gets a call from Rose, who tells them about Elena's plan to give herself over to Klaus. The Travelers know a spell that can temporarily deactivate them and cause vampires to burn in the sun even with the jewellery on. Damon Salvatore is a vampire, turned by Katherine Pierce 145 years prior to the series' debut. He is the son of late Giuseppe Salvatore, ripper Lily Salvatore and older brother of Stefan Salvatore. Damon is portrayed as charming but cruel, taking pleasure in killing and feeding on humans, while Stefan satisfies his vampiric hunger by feeding on animals. It was probably lost when Klaus broke his curse and transformed into a wolf for the first time in over a thousand years.

At Salvatore's mansion they bring a desiccated Silas, to trade Silas's life with Bonnie he must become mortal (witch). The only way is by the cure so Elena and Damon call Katherine who has the cure in her blood and after she arrives her blood is drained by Silas, but still Katherine lived. Amara is then awakened and revealed to be the mystic anchor. She then cures herself of her immortality by feeding off Silas. As soon as Amara is awakened, she wants to die. Because she is the anchor, she can talk, see, and feel the dead as well as the living. Amara has mental problems and tries numerous attempts to kill herself. In Promised Land, it has been four days since the travelers took Stefan and Elena and Damon has been desperately searching for them. He is torturing a Traveler inside a guy named Sykes. He asks him where Markos is as the Travelers want to break the witch curse so they can settle, it also reverses the witch's spell that created vampires and they all die. Damon ungags the Traveler long enough for him to say there's nothing they can do to stop Markos. Later, he gets a call from Stefan who informs him that he and Elena have managed to free themselves from the Travelers but don't know where they are. When Stefan tells him that he has Elena hunting squirrels, Damon jokes that Elena will shoot Stefan's eyes. Damon tells him that he will find and kill Markos and asks him to have both him and Elena return home safely. Before Damon can figure out what's happening, Rebekah's within kissing distance. She greets him as her lover. She then stabs Damon in the gut. Damon dreams that Elena has come to save him. When he wakes, he realizes that Rebekah planted the dream in his mind. Once he finds out about the bloodline issue, Stefan marches over to Klaus. He drops a bag filled with eight of the remaining daggers on the floor, tells them Finn is dead, and offers to trade the weapons for Damon. It sounds too easy but Klaus compels a nearly drained Damon to go home. Before Damon amputates his own hands in an attempt to free himself from the chains, Klaus tells Damon to stop. Then, he compels Damon to tell him how many stakes really exist and Damon tells him the truth that there are eleven. The witch who casts the enchantment can also temporarily or permanently undo the spell on the jewelry at their discretion.

In a flash-forward scene, a medical student Elena is seen writing on her diary outside the Salvatore crypt in the cemetery, while a crow flies over her head as she sees Damon. The scene is a nod to the cemetery scene in the show's pilot episode of season 1 when Damon can control fog and crows. They are also revealed to be married, growing old, and finding peace together. As Elena reunites with her family in the Gilbert house, Damon reunites with Stefan in the Salvatore Boarding House with the words, "Hello, brother." This line is both his first and last words in the entire series. Damon woke up in the shed without his daylight ring. Stefan wanted to know what Damon was really doing there and Damon said he wanted to feel a connection to his humanity again. He tried to convince Stefan to go on a road trip with him. Instead, Stefan reminded Damon of all the times he had ruined his life and how he could not seem to help but do it. Damon got that there would be no road trip for them. The season ended with Damon and Enzo get taken by an unknown creature in a vault. Concluding in a cliffhanger, the next season reveals what really happened to Damon and Enzo. Later, Damon along with Stefan is waiting for Elena to wake up. Damon tells Stefan that he plans on to tell Elena everything he did in her absence and is ready to face the consequences. He's determined not to be another Katherine and spend his whole life running. Elena then wakes up and Damon smiles at her. Elena greets Damon happily and assures him that its really her. It is then revealed that Katherine injected Elena's body with the enhanced Ripper Compound that Wes had made making Elena a vampire ripper just like Damon. Elena takes the cure and, unexpectedly, her memories return and she remembers when she had traveled to Nova Scotia with Damon in search of the cure the first time, he'd told her that he used to miss being human, but, now, he could not imagine anything more miserable. She tells him he needs to think about it before making that decision and enlists Stefan to try to make sure Damon is certain of his choice to become human. Damon almost decides he'd rather stay a vampire until he witnesses an interaction between an older couple. Before Jo and Ric's wedding, he tells Elena he'd made his choice to live one lifetime with her. During the wedding, Kai shows up and stabs Jo before causing an explosion. The second to last episode ends with Elena lying unconscious on the ground.In Know Thy Enemy, Damon and Stefan are rushing downstairs, discussing why Isobel would show up on Elena's doorstep. Katherine tells them not to reveal her presence in Mystic Falls, because it would be easier to keep ‘swapping places' with Elena if no one knew about her. Damon, Bonnie, and Jeremy go to Jonas Martin's apartment, where she tells Damon that if she can find the place where the witches were burned, she can harness their power. Damon's also in the living room when Katherine asks them all about their plan, which they refuse to tell her. Damon, Jeremy, and Bonnie later go to the Witch Burial Ground, where a mansion stands. As soon as he enters, Damon finds that the spirits there are vicious toward vampires, and they temporarily disable his ring so the sun will burn him. He manages to get out before he's burned too badly. While Bonnie and Jeremy work inside the house, he hovers on the porch. When he tries to enter, the door slams shut of its own accord. In We'll Always Have Bourbon Street, Damon awakens the morning after he and Elena finally consummated their relationship. He admits to Elena that he's happy, and they have sex again. When Elena leaves for school, Damon makes one request -- that they wait just one day before they tell Stefan about them. Stefan arrives just as Elena is leaving, and he confronts Damon with his theory about the sire bond. Damon resents Stefan for suggesting it and wants to dismiss it completely, but Stefan only asks that Damon test the theory by asking Elena to try drinking from a blood bag again, and to emphasize that it would make Damon happy if she did. Damon reluctantly agrees to try, though he makes it clear that if Stefan is wrong, he should be very sorry indeed. Damon meets Elena at school and gives her a blood bag. She's doubtful that it will work, but when she is able to drink it without a problem, she's thrilled. With the sire bond seemingly confirmed, Damon is dismayed, though he doesn't let on to Elena what is going on.