In 1930, during Prohibition, reigning crime kingpin Al Capone supplies illegal liquor and has nearly the entire city of Chicago under his control. Bureau of Prohibition agent Eliot Ness has been tasked with bringing a stop to Capone’s activities, but his first attempt at a liquor raid fails due to corrupt policemen tipping Capone off. He has a chance meeting with a veteran Irish-American officer, Jim Malone, 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 yet come under Capone’s influence, and still believes in the “doing some good” aspect of law enforcment. They recruit Italian-American trainee George Stone (AKA Giuseppe Petri) for his superior marksmanship and integrity. Joined by accountant Oscar Wallace, 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 person in charge of the cache as a warning to his other subordinates.
Wallace discovers that Capone has not filed an income tax return for four years and suggests that the team try to build a tax evasion case against him (as Capone’s network keeps him well-insulated from his other crimes). An alderman offers Ness a bribe to drop his investigation, but Ness angrily refuses it. After Capone enforcer Frank Nitti threatens Ness’s family, Ness immediately moves his wife and daughter to a safe house. In a subsequent raid on the Canadian border, Ness and his team intercept an incoming liquor shipment. They kill several gangsters and capture a Capone bookkeeper named George, whom they eventually persuade to collaborate. Back in Chicago, as Wallace escorts George from the police station to a safe house, a disguised Nitti shoots both of them dead. Ness confronts Capone at the Lexington Hotel after the murders, but Malone intervenes to save him, urging Ness to focus on persuading the district attorney not to dismiss the charges against Capone.
Malone realizes that police chief Mike Dorsett sold out Wallace and George, and, in a fight with Dorsett, forces him to reveal the whereabouts of Capone’s head bookkeeper, Walter Payne. That evening, Malone is lured outside his apartment by a Capone underling, and Nitti critically wounds him in a Tommy gun ambush. Ness and Stone arrive at the apartment; before dying, Malone shows them which train Payne is taking out of town. As Ness and Stone await Payne’s arrival at Union Station, they see a young mother with two suitcases and a child in a carriage laboriously climbing the lobby steps. Ness ultimately decides to assist her, but the gangsters who are guarding Payne appear as Ness and the woman reach the top of the stairs, and a bloody shootout takes place. Though outnumbered, Ness and Stone manage to capture Payne alive and kill his escorts without harm to the mother or the child.
Later, when Payne testifies at Capone’s trial, Ness observes that Capone appears strangely calm and that Nitti is wearing a gun in the courtroom. The bailiff removes Nitti and searches him, discovering he has a permit from Chicago’s mayor, William Hale Thompson, which allows him to carry the weapon legally; however, Ness finds a matchbook containing Malone’s address in Nitti’s possession and realizes that Nitti is Malone’s killer. Panicked, Nitti shoots the bailiff before fleeing to the courthouse roof. Ness gives chase and, upon Nitti’s verbal provocation, pushes Nitti off the roof to his death.
Stone gives Ness a list, taken from Nitti’s coat, which shows that the jurors in the trial have been bribed. At Ness’s request, the judge subsequently orders that the jury in the Capone trial be switched with that of an unrelated divorce trial in the adjacent courtroom. This prompts Capone’s lawyer to enter a guilty plea despite his client’s enraged protests. Capone is found guilty of tax evasion and sentenced to eleven years in prison. On the day Capone begins serving his sentence, Ness closes up his office and gives Malone’s St. Jude medallion and callbox key to Stone as a farewell gift. As Ness leaves the police station, a reporter mentions the probable repeal of Prohibition and asks Ness what he will do in that case. Ness replies, “I think I’ll have a drink.”