Darla: Angel was sired by Darla. The pair were lovers until Angelus' transformation into Angel drove them apart, although he briefly tried to stay with her. She was regarded by Angel as his 'obsession', and even with a soul, knowing what she was and what she had done, he was still attracted to her in some way. During Darla's brief moments of humanity - when she is resurrected by Wolfram and Hart - the two retain a close bond, with Angel risking his life to give her a second chance. When Darla becomes pregnant with her and Angel's son, Connor, Darla stakes herself to allow Connor to be born, asking Angel to tell the child that their son was the only good thing they ever did together.

Drusilla: Angelus tormented the human Drusilla, sired her and kept her on as a companion afterwards; Angelus regarded her as his greatest work. The two also have a sexual relationship many years later during a period when her lover, Spike, is wheelchair-bound.

Buffy Summers: Angel's "first love." When he first sees Buffy, he realizes that he wants to be someone. When they sleep together for the first time, Angel loses his soul, becoming Angelus. Buffy is forced to kill him, to save the world, even though Willow has just ensouled him. After he returns from Hell, he and Buffy still love each other, and attempt a relationship. After realizing this relationship is unfair to Buffy, he leaves. Buffy comes to L.A, and for a brief time, Angel becomes human. He has to rewind the day, because being human will eventually lead to Buffy's death without him able to fight at peak performance. After Buffy dies in the fifth season of Buffy the Vampire Slayer, Angel spends months away at a convent in Asia. He comes to help Buffy in the Buffy finale, and they have an emotional conversation. Angel provides aid to Buffy in the final fight against Caleb, gives her an amulet that proves important in the final confrontation with the First, and goes to seek Buffy out in Italy during the last season of Angel, albeit unsuccessfully. He feels that he and Buffy share a "forever love."

Kate Lockley: Kate serves as Angel's contact in the police force as he starts his private detective business. The strong possibility of a relationship is hinted at, but ultimately doesn't materialize as she is unable to accept her discovery of his vampire nature, blaming him for the death of her father when her father was killed by vampires and wouldn't invite Angel in to help.

Rebecca Lowell: A short-lived potential love interest introduced in the episode "Eternity", Rebecca is an actress who hires Angel as her bodyguard. Learning about his vampire nature, she tries to convince him to turn her, not wanting to become old and unattractive, but her attempts only result in Angel briefly reverting to Angelus when she drugs his drink, inducing a feeling of bliss. After this, she leaves the office and is never seen again.

Winifred Burkle: After he rescues her from the Pyleans during their first meeting, Fred develops a childlike crush on Angel for a time; she gets over it after learning more about the curse, but later kisses Angel as part of a ruse to escape Jasmine's followers. She remains the only person to have seen Angel's demonic side before she knew who he was and not been scared by it, creating a close bond between the two of them even without a romantic relationship.

The Transuding Furies: The Furies are the three beautiful, powerful beings who cast the anti-demon-violence spell on Lorne's bar, Caritas. When Angel needs the spell removed to fight Gunn's rogue former gang, the Furies tell Cordelia that they will require 'payment' for such an act, and only Angel is 'equipped' to repay the debt (Whenever he is mentioned all three of them say, "Mmmm... Angel"). The general tone seems to imply a past sexual relationship between the Furies and Angel.

Cordelia Chase: Friends for years, Angel and Cordelia eventually realize that they have fallen in love with one another, only to be torn apart by her ascension and transformation and his imprisonment underwater by Connor before they can tell each other. Upon their subsequent returns, they do not pursue the relationship; Cordelia instead, under the control of Jasmine, forms a relationship with Angel's son, which results in her falling into a coma when Jasmine uses her body to create an independent host for itself. Later, Cordelia returns to put Angel back on track to stopping the Apocalypse. She does this and just before she dies, Cordelia and Angel share their first and only real kiss. In doing so, one last vision, that shows Angel who the true power holders are, is passed to him, helping him to stop the Apocalypse from the inside. The visions can only be passed if the previous owner is in love with the recipient. Even though they never properly tell each other, they both know how each other felt. Cordelia died knowing that Angel knew her feelings.

Gwen Raiden: A thief with command over electricity, Angel shares a kiss with Gwen after she gives him an electro-shock that (temporarily) reawakens his dead heart. He subsequently flirts with her to make Cordelia jealous while they are trying to protect the Ra-Tet from the Beast, but later seems to develop a slight affection for her; he almost appears jealous when she asks for Gunn's help over his.

Nina Ash: A werewolf who Angel saves from being eaten, she develops feelings for Angel and he is eventually convinced to give a relationship a shot. This relationship establishes that Angel is able to have positive sex (unlike his "perfect despair" moment with Darla) and still keep his soul.

Eve: Angel's liaison to the Senior Partners, she and Angel have a one-time encounter at Wolfram & Hart's Halloween party, when Lorne loses control of his empathic powers and he begins to unintentionally write destinies instead of reading them (he tells Angel and Eve to "get a room", saying that "you could cut the sexual tension with a knife"). When Angel thinks they should talk about it, Eve remarks, "It's not as if this is the first time I've had sex under mystical influence. I went to UC Santa Cruz". After this, however, their relationship becomes increasingly hostile due to Eve's relationship with Angel's old foe Lindsey, particularly following her attempt to infect Angel with a dream-inducing parasite.

Faith Lehane — When Faith first crosses the line by killing a man, Angel is the first person to attempt to rehabilitate her. However, he is interrupted when Wesley tries to hand her over to the Watchers Council. While working for Mayor Wilkins Faith attempts to remove Angel's soul by seducing him. At this point Faith harbors a primal sexual attraction to Angel, but this is never elaborated on after she falls into a coma. After awakening from her coma and fleeing Sunnydale Faith goes to Los Angeles. Shortly after her arrival Wolfram and Hart hire Faith to kill Angel. After torturing Wesley, Angel confronts Faith, and during the fight he realizes what Faith really wants; she wants Angel to kill her. He refuses, and again tries to help her, defending her from both Buffy and agents of the Watcher's Council. Thanks to Angel's help Faith starts down the path to redemption by confessing to her crimes and going to prison. He visits her to make sure she is alright and prison is where she stays for several years. She later breaks out, but only because Angel needs her help, due to Angelus having been restored. Despite the difficulties involved in such a task, Faith makes sure he is brought in and protected so he can be re-ensouled by Willow, even defeating Connor to prevent him from staking his father. The two share a strong bond based on their mutual desire for redemption; Faith also states that Angel is the one person that has never given up on her, a factor that doubtless plays an important role in her decision to fight so hard to save him.

Willow Rosenberg - Angel shares deep affection and mutual confidence with Willow. And not just because she restored his soul not once but twice. In several occasions he asks for her help, looking at her as a reliable ally and friend. At the end of episode "Orpheus" (the last time they meet onscreen) they hug as very good old friends.