Brooklyn, New York 1969. A group of four boys walk up to Bleek Gilliam (Zakee L. Howze)'s brownstone rowhouse and ask him to come out and play baseball with them. Bleek's mother insists that he continue his trumpet lesson, to his chagrin. His father becomes concerned that Bleek will grow up to be a sissy, and a family argument ensues.
In the end, Bleek continues playing his trumpet, and his friends go away. 20 years later. The adult Bleek Gilliam (Denzel Washington) is performing on the trumpet at a busy nightclub with his jazz band, The Bleek Quintet. They make up of trumpeter Bleek, saxphone player Shadow Henderson (Wesley Snipes), pianist Left Hand Lacey (Giancarlo Esposito), drummer Bottom Hammer (Bill Nunn), and bass player Rhythm Jones (Jeff "Tain" Watts). Giant (Spike Lee), whom is the Quintet's manager and one of Bleek's former childhood friends, is waiting in the wings, and advises him to stop allowing his saxophone player Shadow Henderson to grandstand with long solos. The next morning Bleek wakes up with his girlfriend, Indigo Downes (Joie Lee). She leaves to go to college classes, while he meets his father by the Brooklyn Bridge for a game of catch, telling him that while he does like Indigo, he likes other women too and is not ready to make a commitment.
Later in the day while he is practicing his trumpet, another woman named Clarke Bentancourt (Cynda Williams) visits him. She suggests he fire Giant as his manager; he suggests that they make love (which he refers to as 'mo better'). She bites his lip and he becomes upset about it, saying, "I make my living with my lips," as he examines the bleeding bottom lip. Giant is with his bookie, betting on baseball. Then he goes to the nightclub and argues with the doormen about what time to let the patrons into the club.
He meets Bleek inside with the rest of the band, except for the pianist, Left Hand Lacey, who arrives late with his French girlfriend and is scolded by Giant. Later Giant goes to the club owners office, points out how busy the club has been since Bleek and his band began playing there, and unsuccessfully attempts to renegotiate their contract. The next morning, Giant meets his bookie (Ruben Blades), who is concerned that Giant is going too deep into debt. Giant shrugs it off, and places several new bets.
He then stops off at Shadow's home to drop off a record. Shadow confides in him that he is cheating on his girlfriend. This leads to the next scene where Bleek is in bed with Clarke, and she asks him to let her sing a number at the club with his band, to which he declines. Bleek and Giant are fending off requests from the other members of the band, especially Shadow, for a raise due to the bands success at the club. Bleek goes to the club owners to see about more money, which they refuse, reminding him that it was Giant who locked him into the current deal. That night at the club, both Clarke and Indigo arrive at the club to see Bleek. They are wearing the same style dress, which Bleek had purchased for them both.
Bleek attempts to work it out with each girl, but they are both upset with him over the dresses, and though he sleeps with them each again they leave him (after he calls each of them by the others' name). However, tension rises with Shadow, who has feelings for Clarke. Bleek and Giant go for a bike ride, where Bleek insists to Giant that he do a better job managing and bringing in money. Giant promises to do so, then asks Bleek for a loan to pay off his gambling debt.
Bleek declines, and later Giant is apprehended by two loan sharks Madlock (Samuel L. Jackson) and Rod (Leonard L. Thomas) who demand payment. Giant can't pay and gets his fingers broken. Later Giant tells Bleek that he fell off his bike on the ride home, but Bleek does not believe him. Giant asks the other band members for money and Left loans him five hundred dollars. When loan sharks stake out Giant's home, he goes to Bleek for a place to stay. Bleek agrees to help him raise the money, but fires him as manager.
Bleek misses both his girlfriends, leaving messages for each, but Clarke has begun a new relationship with Shadow. Bleek finds out about it, and fires Shadow from the band. The loan sharks track Giant down at the club before Bleek can come up with the money, take him outside and beat him while Bleek plays. Bleek goes outside to intervene, and gets beaten as well. Additionally, one loan shark (Madlock) takes Bleek's own trumpet, and smacks him across the face with it.
This not only puts Bleek in the hospital, but it also permanently injures his lip, making him unable to continue playing trumpet. Months later, Bleek reunites with Giant, who has gotten a job as a doorman and stopped gambling. He drops into see Shadow and Clarke, who are now performing together with the rest of Bleek's former band. Shadow invites him on stage, and they play together. Bleek still has scars to his lips, and is unable to play correctly. He walks off the stage, gives his trumpet to Giant, and goes directly to Indigo's house. She is angry with him because she hasn't heard from him in over a year. She tries to reject him, but agrees to take him back when he begs her to save his life.
A montage flashes through their wedding, the birth of their son, Miles (Jelani Asar Snipes), and Bleek teaching his son to play the trumpet. In the final scene of the movie, Miles (Arnold Cromer) is ten years old, and wants to go outside to play with his friends. Indigo wants him to finish practicing his trumpet lessons. However, Bleek relents and allows his son to leave and play. This final scene uses exactly the same dialogue as the (almost identical) opening scene, with changes only in the delivery of the dialogue leading to an alternate conclusion.