Michael Sullivan Sr. (Hanks) is an enforcer for Irish mob boss John Rooney (Newman) in Rock Island, Illinois during the Great Depression. Rooney raised the orphan Sullivan and loves him more than his own biological son, the unstable Connor (Craig). Connor snaps and kills disgruntled associate Finn McGovern when meeting him with Sullivan, resulting in Sullivan gunning down McGovern's men. Sullivan's twelve-year-old son Michael Sullivan, Jr had hidden in his father's car and witnesses the event. Despite Sullivan swearing his son to secrecy and Rooney pressuring Connor to apologize for the reckless action, Connor murders Sullivan's wife Annie and younger son Peter, mistaking him for Sullivan, Jr. He then sends Sullivan to an ambush at a speakeasy but Sullivan realizes and escapes to Chicago with his son to seek Al Capone, for work and to discover the location of Connor, who has gone into hiding.
In 1973, Sam "Ace" Rothstein (Robert De Niro) is a sports handicapper and Mafia associate who is sent to Las Vegas to run the Teamsters Union-funded Tangiers Casino on behalf of the Chicago Outfit. He hires old friend Billy Sherbert (Don Rickles) as his manager. In between, Ace and his friend, mob enforcer and caporegime Nicholas "Nicky" Santoro (Joe Pesci), narrate how the mob bosses control the Teamsters Union, which gives out money for casinos that they own, such as The Tangiers, and how they also drive off rival crews and get rid of cheaters. Ace becomes the Tangiers' de facto boss by taking advantage of lax gaming laws allowing him to work at the casino while his gaming license is still pending. He doubles the casino's profits, which are skimmed by the Mob before the records are reported to income tax agencies. The bosses are impressed with Ace's work and send Nicky to protect Ace and the whole business, along with Nicky's brother Dominick, Nicky's friend and subordinate Frank Marino (Frank Vincent), and the rest of Nicky's soldiers in his crew. Nicky, however, becomes more of a liability than an asset; his criminal activities- which he makes nearly no effort to conceal- and his violent and vicious temper quickly gets him banned by the gaming board from every casino, and his name is placed in the Black Book. In retaliation, Nicky gathers his own crew, opens a jewelry store and restaurant, begins running unsanctioned shakedowns and burglaries, and soon after is considered the mob boss of Vegas.
During Prohibition in 1930s, Al Capone (De Niro) has nearly the whole city of Chicago under his control and supplies illegal liquor. Bureau of Prohibition agent Eliot Ness (Costner) is assigned to stop Capone, but his first attempt at a liquor raid fails due to corrupt policemen tipping Capone off. He has a chance meeting with Irish-American veteran officer Jimmy Malone (Connery), who is fed up with the rampant corruption and offers to help Ness, suggesting that they find a man from the police academy who has not come under Capone's influence. They recruit Italian-American trainee George Stone (Andy García) for his superior marksmanship and intelligence. Joined by accountant Oscar Wallace (Charles Martin Smith), assigned to Ness from Washington, D.C., they conduct a successful raid on a Capone liquor cache and start to gain positive publicity, with the press dubbing them "The Untouchables." Capone later kills the henchman in charge of the cache as a warning to his other men.
Ambitious politician Walter Chalmers (Robert Vaughn) is about to present a surprise star witness in a Senate Subcommittee hearing on organized crime. The witness, Johnny Ross (Pat Renella), a defector from the Organization in Chicago, is put under San Francisco Police Department protective custody for the weekend, 40 hours until his Monday morning appearance.
Jimmy Hoffa and Bobby Ciaro are impatiently waiting in the parking lot of a roadhouse diner on July 30,1975. Others are late for a meeting. Asked if he wants to leave, Hoffa gives Ciaro a scornful glance. The first flashback to 1935 then occurs:
Truman Gates (Patrick Swayze), raised in Appalachia, has migrated to Chicago to become a police officer. Married to Jessie, who has a baby on the way, he seems to have made the transition from hillbilly to respectable law man. When the local coal mine closes, Truman persuades his younger brother Gerald (Bill Paxton) to look for work in Chicago. But things take a turn for the worse when soon after landing a job as a truck driver, Gerald's vehicle is hijacked by mobsters and Gerald is killed by Joey Rosellini (Adam Baldwin), the nephew of mob boss Poppa John Isabella (Andreas Katsulas).
Frank (James Caan) is a highly experienced jewel thief and hardened ex-convict who has a set structure to his life. With a pair of successful Chicago businesses (a bar and a car dealership) as fronts for his lucrative criminal enterprise, Frank sets out to fulfill the missing part of his life vision: a family beginning with Jessie (Tuesday Weld), a pretty cashier he has begun dating.
An organized crime war breaks out between two rival gangs in Chicago during the Roaring Twenties. The leader of the Southside Mob is the notorious Al Capone, who resents his nemesis George "Bugs" Moran's activity in the city. Moran, too, wants control of the town's bootlegging and gambling operations. His lieutenants Peter and Frank Gusenberg use threats and intimidation to make tavern owners do business with them in exchange for "protection." Moran gives the order to have a crony of Capone's eliminated as the Chicago body count escalates. Inclusive are flashbacks to a lunchtime attack on Capone at a restaurant outside of Chicago by Hymie Weiss and Moran in September 1926 and the murders of Weiss in October 1926 and Dion O'Banion in November 1924 by Capone's gang.
At a loading dock in Cleveland, Ohio in 1937, supervisor Mr. Gant welcomes a new worker, Lincoln Dombrowsky (Frank McRae). Gant tells him the job requirements and pay rules. He'll be paid for working 8 hours and if he has to work overtime, he still gets paid only for 8 hours. If he drops any of the merchandise, the cost comes directly out of his pay. These are examples of unfair working practices faced by the laborers. Later Dombrowsky drops a few carts of tomatoes, which is taken out of his pay; another worker is fired for helping him collect the fallen merchandise. Johnny Kovak (Sylvester Stallone), another worker resentful of mistreatment, leads a riot. Afterward, the workers go to the office of Boss Andrews. Kovak believes he negotiates a deal for the workers, but the next day he and his friend Abe Belkin (David Huffman) are told they are fired.
Two hitmen drive to Eddie Macklin's house to assassinate him as he builds a brick wall in his backyard. Meanwhile, Eddie's brother Earl (Robert Duvall) is released from prison in Illinois after a 27-month term for carrying a concealed weapon. His girlfriend Bett (Karen Black) picks him up and takes him to a motel. She informs Earl of his brother's execution by the Outfit. Earl deduces that the motel stay is a setup, and when one of the hitmen who killed his brother bursts into the room, Earl ambushes him and tortures him for information.
Lou Marazano was once a feared hit man, but his reputation has dimmed significantly twenty years after his retirement. Unable to help his daughter financially after her ex-husband fails to pay child support, he asks the street boss, Lorenzo Galante, for work. Though reluctant to give him the job, the mob sends him to kill several witnesses who will testify against a corrupt labor leader. After Marazano sends flowers to the widow of one of the men he kills, Ray Berkowski, a veteran cop, reopens a case that involved a string of murders from the early 1990s. Though discouraged from investigating, Berkowski and his partner, Ralph Maloney, stake out the second target. Picked up at the scene of he crime, Marazano does not talk, and the police are forced to set him free when his girlfriend and her neighbors provide an alibi.