Damon gains Liz's trust during Season 1 and part of Season 2. He pretends to help her track down and kill the vampires in Mystic Fall to cover up his tracks and make sure that they don't suspect that him and his brother are vampires.Damon and Liz became good friends and Liz has even called Damon her "closest ally". Now that she knows that he is a vampire like her daughter, the status of their relationship is unknown. It seems now that Liz has come to terms with Damon's vampire nature and accepts him, although she's still not too keen on vampires as a whole. Quite frankly Liz doesn't know that Damon abused her daughter.
Damon wins Liz over when he saves her from being attacked by Lexi, another vampire, who came to town to celebrate Stefan's birthday. Damon also supplied her with vervain to protect herself, her deputies and the Town Council although his plan was to infiltrate the council. Damon also saves Caroline from Logan who blackmails Liz. Despite his previous involvement with Caroline, Liz puts her trust in him unaware that he is a vampire.
Damon tries to comfort Liz at the hospital after Caroline accident.She also informs him about Richard Lockwood's death unaware that Damon already knows about the incident.Later, when an argument breaks out between Elizabeth and Carol,Damon intervenes and reminds them they are on the same side and the protection of the Town is their priority.
Later, in Kill or Be Killed, Mason reveals to Liz that Damon and Stefan are vampires. She denies this immediately, but Mason proves it by spiking a cup of lemonade with vervain. Liz watches Damon drink and gag on the vervain saturated lemonade. Later, Damon, who is furious at Mason for spiking the lemonade, attempts to kill him together with Stefan, falling right into Elizabeth's trap. The Salvatore brothers are shot several times with wooden bullets, and dragged to the underground chamber, where Elizabeth tortures them to get information. Damon refuses to give anything, while Stefan is unconscious, and Elizabeth orders to have them staked. Damon asks why Liz is doing this, as they were friends. Elizabeth replies that the friendship was a lie and shoots him again. Just before the Salvatore's were about to be staked, Caroline and Elena arrive and Caroline drains a deputy of blood, and kills another. Beside herself from her daughters revelation, when Damon threatens to kill Liz, Liz begs him to out of mercy, because she cannot stand the idea of her daughter being a vampire.
Damon yanks Elizabeth up, but does not hurt her, saying that they were still friends. He intends to hold her captive at the Salvatore Boarding House until the vervain wears off and he will be able to compel her. Caroline later compelled her to forget that she, Stefan and Damon were vampires once the vervain wore off.
In The Descent, she calls Damon to investigate about a series of deaths caused by a vampire, (Rose). Damon staked Rose who was already dying of a werewolf bite, out of mercy. Damon later presented the body to Liz saying he would bury it himself.
Elizabeth tried to kill Damon who, after being bitten by Tyler, was delusional. Damon escaped and Elizabeth had to imprison Elena in her office, but in her attempt to shoot him, he fled and she shot Jeremy, who was standing behind Damon, instead.
In Disturbing Behavior, Liz asks Damon to help her deal with Bill whom she had locked up in the same cell where he held Caroline.
In 1912, she arrests Alaric as a suspect of murder, and tells him of the evidence against him and Damon tries to convince her that Alaric is not the killer, but she threatens to lock Damon up as well.
In Memorial, Liz asks Damon if he played a role in the explosion causing the deaths of the town council members. He tells her he didn't, and snarkily replies that, if he had wanted to kill them, he would have fed from them and not caused an explosion to happen.
In The Walking Dead, Liz calls Stefan and Damon to the hospital and explains that the hospitals kept the blood banks empty ever since they were raided thinking that it keep the vampire population away. She then shows the bodies completely drained of blood and asks them if they think its Silas, Damon jokes about it being a doctor with questionable bedside manners and Liz says five victims is a lot of blood and Silas can't take it with him. Liz asks for an explanation since she is dealing with five grieving families and a psychic killer on the loose.They bring Liz up to speed by telling her Silas' plan to drop the veil to the other side and take the cure and die and not spend an eternity in a supernatural purgatory and when he plans on doing it. Later Liz is still at the hospital with Stefan and Damon with power out and she explains where the power outrage originated from.
In No Exit, Elizabeth helps Caroline to track down Damon.
- Liz: "Keep Caroline away from me, please. I don't want to see her."
- Damon: "She's your daughter, Liz."
- Liz: "Not anymore. My daughter's gone."
- Damon: "You have no idea how wrong you are about that."
- -- Kill or Be Killed
- Damon: "So Mayor Lockwood called your gay ex-husband to torture your vampire daughter?"
- Liz: "Yes. I've been keeping him detained to make sure the vervain's out of his system. So you could, you know..."
- Damon: "Can't we just kill him?"
- Liz: "No, Damon! He's Caroline's father."
- Damon: "He sounds like a douche-bag to me."
- Liz: "Yeah, well, just 'cause you and I are on OK terms doesn't mean that I'm a suddenly a big advocate for your "lifestyle.""
- Damon: "Is that what you told him when you two got divorced?"
- -- Disturbing Behavior
- In Family Ties, Liz first saw Damon at the Founder's Ball with her daughter.
- Damon has dated Liz's daughter Caroline.
- Liz starts to rely on Damon after he kills Lexi in 162 Candles.
- Liz tried to kill Damon twice.
- When Liz started to hate her daughter, as she was a vampire, Damon tried to convince her to stay normal with her daughter.
- Disturbing Behavior, Liz asks Damon to help her deal with Bill whom she had locked up in the same cell where he held Caroline.
- In True Lies, Liz helps Damon to find out Stefan.
- In 500 Years of Solitude, Elizabeth stopped Damon when he tried to suffocate Katherine with a pillow stating that it's still a crime and if he continued she'd of arrested him.
- In Man on Fire, Liz gives Damon information about Maggie James's death.
- In Home, Liz was saved by Damon.