Holden McNeil (Ben Affleck) and Banky Edwards (Jason Lee) are comic book artists and lifelong best friends. They meet fellow comic book artist Alyssa Jones (Joey Lauren Adams) at a comic book convention in New York City, where they are promoting their comic Bluntman and Chronic. Holden is attracted to Alyssa, but soon learns that she is a lesbian. The two begin spending time together, and a deep friendship develops. Eventually, Holden is no longer able to contain his feelings, and confesses his love to Alyssa. She is initially angry with him, but that night, the two sleep together and begin a romantic relationship.
This new development worsens the tension between Holden and Banky, as Banky resents Alyssa for coming between him and his best friend. He investigates and uncovers dirt on Alyssa’s past, and he reports to Holden that Alyssa participated in a threesome with two boys during high school, who gave her the nickname “Finger Cuffs”. Holden is deeply upset by this revelation, having previously believed that he was the first man Alyssa had ever slept with. While attending a hockey game, he clumsily attempts to bait her into confessing, and in response she angrily boasts of having had the threesome in question, loudly enough for everyone within earshot to hear. During the argument that ensues, she tearfully tells Holden about her “many” youthful sexual experimentations, and refuses to apologize for her past. Holden leaves feeling disillusioned and furious.
Later, during lunch with Jay and Silent Bob (Jason Mewes and Kevin Smith), Silent Bob reveals that he was once in a relationship similar to Holden’s. Despite the fact that he was in love with his girlfriend, Amy, his neurosis about her adventurous sexual past led him to end the relationship. Later realizing that this was wrong decision, he says he has “spent every day since then chasing Amy, so to speak.”
Moved by Silent Bob’s story, Holden devises a plan to fix both his relationship with Alyssa and his estranged friendship with Banky. He invites them both over and tells Alyssa that he would like to get over her past and remain her boyfriend. He also tells Banky that he realizes that Banky is in love with him—kissing him passionately to prove the point. Holden suggests a threesome. Though initially shocked, Banky agrees to participate, but Alyssa refuses, explaining to Holden that it will not save their relationship. Before leaving, she states that she will always love him, but she will not be his “whore.” Banky then leaves the room without saying a word.
One year later, both Banky and Alyssa are busy promoting their own respective comics at a convention in New York. It is revealed that Holden and Banky dissolved their partnership on Bluntman and Chronic, the rights to which Holden now exclusively owns. Banky smiles sadly at seeing Holden, who silently congratulates him for his success on his own solo comic. Banky gestures over to a booth hosted by Alyssa, and provides wordless encouragement to Holden to go talk to her. He has a brief, quietly emotional conversation with Alyssa, and gives her a copy of Chasing Amy, his new comic based on their relationship. After Holden leaves, Alyssa’s new girlfriend (Virginia Smith) arrives and asks who she was talking to. A shaken, misty-eyed Alyssa replies, “Oh, just some guy I knew.”