In Lebanon, Hezbollah militants escort producer Lowell Bergman (Pacino) to Hezbollah founder Sheikh Fadlallah, where Lowell convinces him to be interviewed by Mike Wallace (Plummer) for CBS show 60 Minutes. In Louisville, Kentucky, Jeffrey Wigand (Crowe) packs his belongings and leaves his Brown and Williamson office, returning home to his wife Liane (Venora) and two children, one of whom suffers from acute asthma. When Liane asks about the boxes in Wigand's car, he reveals that he was fired from his job that morning.
Returning home to Berkeley, California, Bergman receives an anonymous package containing documents relating to tobacco company Philip Morris, and approaches a friend at the FDA for the name of a translator. Bergman is referred to Wigand, and calls him at his home only to be steadfastly rebuffed. Curious with Wigand's refusal to even speak to him, Bergman eventually convinces him to meet at the Seelbach Hotel in Louisville. In the privacy of their hotel room, agrees to translate the tobacco documents, but stresses that he cannot talk about anything else because of his confidentiality agreement. After leaving with the documents, Wigand appears at a meeting with Brown and Williamson CEO Thomas Sandefur (Gambon), who orders him to sign an expanded confidentiality agreement, under threat of revoking his severance pay, medical coverage and initiating legal proceedings. Wigand, enraged at the threats and believing that Bergman notified Sandefur about their confidential meeting, calls and accuses Bergman of treachery.
Bergman visits Wigand's house the next day and maintains that he did not reveal anything to Brown and Williamson. Reassured, Wigand talks to Bergman about the seven CEOs of 'Big Tobacco' perjuring themselves to the United States Congress about their awareness of nicotine's addictiveness, and that the CEOs should fear Wigand. Bergman says Wigand has to decide himself whether to blow the whistle on big tobacco. Bergman returns to CBS Headquarters in New York City, where he and Wallace discuss Wigand's situation and the potential damage he could do to Big Tobacco. A lawyer at the meeting claims that Wigand's confidentiality agreement, combined with Big Tobacco's unlimited checkbook, would effectively silence Wigand under mountains of litigation and court costs. Bergman proposes that Wigand could be compelled to speak through a court of law which could give him some protection against Brown and Williamson should he do an interview for 60 Minutes.
The Wigand family move into a newer, more affordable house, and Wigand begins teaching chemistry and Japanese at a Louisville high school. One night while asleep, he's alerted by his daughter to sounds outside the house. Upon investigation, he discovers a fresh shoe print in his newly planted garden, and begins to become paranoid. The next night, Wigand and Bergman have dinner together, where Bergman asks Wigand about incidents from his past that Big Tobacco might use against him. Wigand reveals several incriminating incidents before declaring he can't see how they would affect his testimony. Bergman assures him they will.
Bergman contacts Richard Scruggs (Feore) and Ron Motley (McGill), who with Mississippi's attorney general Mike Moore are suing Big Tobacco to reimburse the state for Medicaid funds used to treat people with smoking-related illnesses. The trio express an interest in Bergman's idea and tell him to have Wigand call them. Meanwhile, Wigand receives death threats via email and finds a bullet in his mailbox, prompting him to contact the FBI, who after subtly accusing him of emotional imbalance confiscate his computer for evidence. Enraged over the threats to his family, Wigand phones Bergman and demands that to fly to New York and tape his testimony immediately. During Wigand's interview with Wallace, Wigand states that Brown and Williamson manipulated nicotine through ammonia chemistry to allow nicotine to be more rapidly absorbed in the lungs and therefore affect the brain and central nervous system through impact boosting. He continues by saying Brown and Williamson have consciously ignored public health considerations in the name of profit.
In Louisville, Wigand begins his new teaching job and talks to Richard Scruggs. Upon returning home, Wigand discovers that Bergman has given him some security personnel. Wigand's wife is struggling under the pressure and tells him so. Days later, Wigand travels to Mississippi, where he receives a restraining order issued by the State of Kentucky to prevent him from testifying. Though the restraining order, issued by Brown and Williamson's lawyers, was thrown out in Mississippi, Wigand is told that if he testifies and returns to Kentucky he could be imprisoned. After a lengthy period of introspection, Wigand goes to court and gives his deposition, during which he says nicotine acts as a drug. Following his testimony, Wigand returns to Louisville, where he discovers that his wife and children have left him.
At this point the film shifts its emphasis from Wigand to Bergman. Bergman and Wallace go to a meeting with CBS Corporate about the Wigand interview. A legal concept has emerged, known as Tortious interference. If two parties have an agreement, such as a confidentiality agreement, and one of those parties is induced by a third party to break that agreement, the party can be sued by the other party for any damages. It is revealed that the more truth Wigand tells, the greater the damage, and a greater likelihood that CBS will be faced by a multi-billion dollar lawsuit from Brown and Williamson. It is later suggested that an edited interview take the place of the original. Bergman vehemently disagrees, and claims that the reason CBS Corporate is leaning on CBS News to edit the interview is because they fear that the prospect of a multi-billion dollar lawsuit could jeopardize the sale of CBS to Westinghouse. Wallace and Don Hewitt agree to edit the interview, leaving Bergman alone in the stance of airing it uncensored.
A PR firm hired by Big Tobacco initiates a smear campaign against Wigand, dredging up details about his life and publishing a 500-page dossier. Through Wigand, Bergman discovers that Big Tobacco has distorted and exaggerated numerous claims, and convinces a reporter from the Wall Street Journal to delay the story until it can be disproven. Bergman contacts several private investigators who do begin their own investigation. Bergman releases his findings to the Wall Street Journal reporter and tells him to push the deadline. Meanwhile, due to his constant fights with CBS management, Bergman is ordered to go on vacation.
Soon after, the edited interview is broadcast. Bergman attempts to call Wigand at his hotel but receives no answer. He instead calls the hotel manager, who opens Wigand's door but is stopped by the deadbolt. Peering into Wigand's room, the hotel manager spies Wigand sitting alone, lost in a daydream about the idyllic life he could have led without his testimony. Per Bergman's commands, the hotel manager convinces Wigand to accept Bergman's phone call. Wigand screams at Bergman, accusing him of manipulating him into his position. Bergman tells Wigand that he is important to a lot of people and that heroes like him are in short supply. After hanging up, Bergman contacts the The New York Times and reveals the scandal that occurred at 60 Minutes, causing the New York Times to release a scathing article. Meanwhile, The Wall Street Journal exonerates Wigand and reveals his deposition in Mississippi, while condemning Big Tobacco's 500-page smear as 'the lowest form of character assassination'. 60 Minutes finally broadcasts the full interview with Wigand.
In the final scene Bergman talks to Wallace and he tells him that he's quitting saying, 'What got broken here doesn't go back together again'. The final shot is of him leaving the building. A series of title cards appear stating the $246 billion settlement that big tobacco made with Mississippi and other States in their lawsuit, that Wigand lives in South Carolina. In 1996, Dr. Wigand won the Sallie Mae First Class Teacher of the Year award, receiving national recognition for his teaching skills. Lowell Bergman works for the PBS show Frontline and teaches at the Graduate School of Journalism at the University of California, Berkeley.