Wesley reappears in the first season of Angel, becoming a cast regular in his second episode "Somnambulist". Introduced as a self-proclaimed "rogue demon hunter", Wesley works with Angel and Cordelia as a member of supernatural detective agency Angel Investigations, serving as a partial replacement for the recently lost Doyle. Comparing the two characters, Denisof states, "Wesley is a clearer counterpart to Angel, whereas Doyle had more street smarts. Although [Doyle] was struggling with his demon nature, he had seen a lot more of the world in the same way Angel had." Nonetheless Denisof believes that in this period, his character "was so anxious to be a tough rogue demon hunter but was clearly a kind of soft puppy dog." Wesley proves his loyalty to Team Angel in the episode "Sanctuary", when, after being tempted with the offer of returning to the Watcher's Council, he betrays his former colleagues in order to help Angel protect Faith, despite the fact that Faith had brutally tortured him in the previous episode.

In Season Two, Wesley finds himself running the organization in Angel's absence during his friend's descent into darkness and shows himself to be highly capable, as well as developing a strong brothers-in-arms relationship with streetwise vampire-hunter Charles Gunn. No longer the coward he once was, Wesley is shot trying to protect Gunn and his friends from a zombie police officer in the episode "The Thin Dead Line", and remains in a wheelchair for the following two episodes. In "Belonging", he seeks his father's approval over being made leader of Angel Investigations, but instead finds his father is more concerned about his next failure following his being fired from the Watchers' Council. Wesley displays the extent of his his ruthlessness when, during an adventure in Pylea, he plans an attack that will send many Pylean rebels to their deaths as part of the rescue of Cordelia from the Covenant of Trombli. As he explains to Gunn when the latter questions his willingness to sacrifice the rebels: "If you try not to get anybody killed, you end up getting everybody killed."

Darker character development

In the third season, Wesley's path soon becomes filled with tragedies and difficult choices. Just as he is beginning to have romantic feelings for teammate Fred Burkle, he is supernaturally influenced to attempt to kill her, ending his immediate opportunity for love (cf. "Billy"). Denisof complimented that episode, "because it was the first real dark change in Wesley to experiment with". After the birth of Angel's son Connor, Wesley becomes convinced by a prophecy that Angel will eventually kill the baby. With the intention of taking him to safety, Wesley betrays his friends by kidnapping Connor. Denisof explains, "It isn't that he's purely bad or purely good, we're discovering a deeper and more complicated area of the character where good and bad aren't as clear, where Wesley does something motivated, he thinks, for the good of all - i.e. saving Connor and relieving Angel of the responsibility of murdering his son - and in doing so creates the situation in which the baby could be kidnapped, Angel loses his son and Wesley has his throat slit for the trouble. So it's grey rather than black or white."

Wesley's plan goes terribly wrong, resulting in his throat cut and the baby being taken to a hell dimension. As Wesley recovers, a furious Angel tries to kill him and he is alienated from his friends. Science fiction magazine Starburst said that "somber, subdued, bearded Wesley is worlds away from the foolish, pompous Wesley". Denisof says of the period, "It was a great opportunity to explore some of the character's darker layers. You couldn't have predicted it when he arrived in Sunnydale. This was an important element to introduce and explore, to be consistent with the show and to continue the organic exploration of all the characters." Whilst the character spent less time with his old friends, Denisof was "more or less isolated from the [main cast], barring one or two scenes of mild confrontation when they would come to visit me and we'd chew each other out. There's definitely a cold war going on with Wesley versus the world."

Wesley continues his descent into self-loathing when he begins a sexual relationship with Lilah Morgan, an employee of evil law firm Wolfram & Hart and Angel's long-time enemy. He forms his own team to fight the good fight, but maintains an interest in the affairs of Angel Investigations. In the opening episode of Season Four, Wesley recues Angel from the bottom of the ocean, reviving him with his own blood. Wesley eventually returns to the team full time during the gang's first confrontation with the Beast and Jasmine's manifestation. Now deeply serious, humorless, and pessimistic, he takes command and makes the difficult decisions of bringing back Angel's evil alter ego Angelus and helping Faith escape from jail in order to stop the Beast. Wesley also has to face the trauma of Lilah's death, particularly when he is forced to decapitate her corpse when it appears she was killed and possibly sired by Angelus (cf. "Salvage"). At the end of the fourth season, Angel performs a powerful mind-wipe which removes certain events from the collective memories of the world at large. Denisof believes that the mind-wipe "selectively erased certain events or adjusted them". After the wipe, Wesley no longer has any recollection of the existence of Connor or the events involving him, but he does know that he went through a dark period of alienation from the group. Wesley's dark attitude is alleviated somewhat when the gang decide to take over Wolfram & Hart. The tension between Wesley and his co-workers did not go away because of the mind-wipe but because "we decided we were better off as a team than as separate entities. And we had to put our differences behind us and build our trust again as a group."