The film opens at a party in Los Angeles, California on March 8, 1997. Just as Biggie Smalls is about to be killed in a drive-by shooting, the film flashes back to Biggie's childhood in Brooklyn, where he (now played by his biological son Christopher Wallace, Jr.) lived during his adolescent years. Biggie, (now played by Jamal Woolard) sells drugs at the height of the crack epidemic, hustling with his friends D-Roc (Dennis L.A. White) and Lil' Cease (Marc John Jefferies).
John Matthews (Dwayne Johnson), owner of a construction company, receives a call from his ex-wife Sylvie Collins (Melina Kanakaredes). His estranged son Jason (Rafi Gavron) is being charged with distribution of narcotics; while Jason is not actually a dealer, his friend set him up in a sting operation to reduce his own sentence after being caught. Jason's charges carry a minimum of 10 years in prison. John feels responsible because he was not there for his son, and becomes desperate as he realizes that Jason may be killed before he finishes his prison sentence.
Francesca "Frankie" Sutton is a Los Angeles bank teller who witnesses a robbery. Shortly after the incident, the bank fires Frankie after the police uncover a connection between her and Darnell, one of the three robbers; despite the fact that Frankie knew nothing of the robbery Darnell had planned. Later, Frankie reunites with her three best friends, Lida "Stoney" Newsome, Cleopatra "Cleo" Sims, and Tisean "T.T." Williams in the projects and is furious because she was fired. Cleo states they should rob a bank themselves to collect all of the money and get out of the projects while being able to have what they want. Frankie agrees, while the other two friends aren't following along with what they are saying. Eventually, Frankie decides to work at a janitorial company with her friends even though they are treated with no respect from their boss, Luther, and receive little pay.
Sean Porter (Dwayne "The Rock" Johnson) works at Kilpatrick Detention Center in Los Angeles. He becomes frustrated at not being able to help the kids get away from their problems in life when they are released from the center, such as street gangs and drug dealings. He decides to create a football team so the kids can feel like they're part of something. Porter believes that football will teach the teenage inmates what it takes to be responsible, mature, and disciplined winners. He picks out a few kids in the room that he feels will benefit from this program and requires that they practice with him the following day. He states to his new team, the Kilpatrick Mustangs, "You do it my way, not your way. Your way got you here and you're here because you lost. Right now you are all losers, but if you accept this challenge and stick with the program, you are all going to be winners at the end." Two of the teens do not get along because they are from rival gangs. Willie Weathers (Jade Yorker) is from the 88’s and Kelvin Owens (David Thomas) is from the 95’s. The first game is against the best team in the league, Barrington. The game starts out somewhat positive for the Mustangs, as they recover a fumble on the first drive, but things quickly turn. They are demolished by Barrington, losing by 38 points. After starting 0–2, the Mustangs start winning games as they learn to work together. Kelvin and Willie finally shake hands when they win a game by one touchdown after Kelvin makes a big block for Willie. Near the end of the season, the Mustangs are headed for the playoffs. They are getting more publicity and more fans along the way.
Conor O'Neill (Keanu Reeves) is a gambler who secretly bets $6,000 on his (dead) father's account and is now severely in debt with two bookies. In order to repay the debts, he is told by a corporate friend that he must coach a baseball team of troubled fifth grade kids from Chicago's ABLA housing projects in exchange for $500 each week, for ten weeks.
Kelly is a struggling young jazz dancer and, through her gay friend Adam, she is introduced to two Street dancers, Ozone and Turbo), who have a bitter rivalry with another crew known as Electro Rock, consisting of poppers Popin' Pete, Poppin' Taco, and Lollipop. They also struggle to overcome scorn from Kelly's dance instructor, Franco, who disapproves of her hybrid dance style and affiliation with street dancers. Kelly soon becomes the sensation of the street crowds. Through it all, the audience is treated to a variety of breakthrough performances, including Turbo's "Broom Scene" and Taco's unique popping solos during the dance battles at the Radiotron nightclub.
Mookie (Spike Lee) is a young black man living in Bedford-Stuyvesant, Brooklyn with his sister, Jade (Joie Lee). He and his girlfriend, Tina (Rosie Perez), have a son. He's a pizza delivery man at the local pizzeria, but lacks ambition. Sal (Danny Aiello), the pizzeria's Italian-American owner, has been in the neighborhood for twenty-five years. His older son Pino (John Turturro) intensely dislikes blacks, and does not get along with Mookie. Pino is at odds with his younger brother, Vito (Richard Edson), who is friendly with Mookie.
Bradley 'B-Rad' Gluckman (Jamie Kennedy) is a young privileged white guy from Malibu, with aspirations of being "the biggest rapper that ever was". B-Rad dresses and speaks like a gangster and essentially thinks and acts like he is black. His father, Bill Gluckman (Ryan O'Neal), is running for governor of California.
The movie begins when a robber (Rickey Smiley), disguised as Santa Claus, breaks into Craig (Ice Cube) and Day-Day's (Mike Epps) house at 3:37 AM on Christmas Eve. Craig fights with the robber, trashing their apartment while making frantic, futile attempts to wake Day-Day. The robber escapes with Craig and Day-Day's Christmas presents and rent money. The same morning, the police come over to get a report.
The plot is centered on two underachieving pot smokers: Silas (Method Man) and Jamal (Redman). When Silas's friend Ivory (Chuck Davis) dies, Silas uses his ashes as fertilizer for a new batch of marijuana. While both are sitting in the parking lot before taking their "THC" (Testing for Higher Credentials, a parody of the SAT in allusion to Tetrahydrocannabinol) exams for college, neither is able to smoke his individual marijuana stash without the help of the other.
In the opening scene, chickens are being prepared for a meal when a chicken escapes and an armed gang chases after it in a favela called the Cidade de Deus ("City of God"). The chicken stops between the gang and a young man named Rocket (Buscapé), who believes that the gang wants to kill him. A flashback traces Rocket, the narrator, back to the late 1960s. He lived incredibly poor in this slum of Rio.
A 20-year-old man named Joseph Summers (Jody) (Tyrese Gibson) lives with his 36-year-old mother Juanita (Adrienne-Joi Johnson), in South Central Los Angeles. He spends most of his time with his unemployed best friend Sweetpea (Omar Gooding), and does not seem interested in becoming a responsible adult. However, he is forced to mature as a result of an ex-con named Melvin (Ving Rhames), who moves into their home. Another factor is his children—a son Joseph "JoJo" Summers Jr. with his girlfriend of five years, 25 year-old Yvette (Taraji P. Henson) and a daughter with a girl that he cheated on Yvette with,18 year-old Peanut, who also lives with her mother.
Craig Jones (Ice Cube), a twenty two year old man living in South Central Los Angeles, California, has just lost his job, after being framed for stealing. Not having any plans, he hangs out on his front porch with his delinquent best friend, Smokey (Chris Tucker), a pothead who sells marijuana for Big Worm (Faizon Love), the psychopathic neighborhood supplier.
Kaydee "Caine" Lawson is a child raised in South Central Los Angeles. His father was a dope dealer who was killed in a drug deal when Caine was ten and his mother was a heroin addict. As a result he went to go live with his grandparents. Caine grows up to become a drug dealer himself along with his friends.
Justice (Janet Jackson) is a young woman living in South Central, Los Angeles. She was named Justice by her late mother, who gave birth to her while attending law school. After the shooting death of her boyfriend Markell (Q-Tip), Justice falls into a deep depression. She spends the majority of her time in the house she inherited from her grandmother, with her cat White Boy, only going out to her job at a local hair salon. Justice is a talented poet, she reads many of her poems throughout the course of the film, both to other characters and in voice over.