A prologue establishes the courage and journalistic integrity of Bergman (Pacino) and Mike Wallace (Plummer) as they prepare to interview Sheikh Fadlallah for 60 Minutes.
In Louisville, Kentucky, Dr. Jeffrey Wigand (Crowe) arrives home from his office at the Brown & Williamson Tobacco Company, reluctantly telling his wife Liane (Venora) that he has been fired.
Bergman approaches Wigand for help translating technical documents. Wigand agrees, but Bergman is intrigued when he cites a corporate confidentiality agreement and refuses to discuss anything further. Wigand is later summoned to a meeting with the B&W CEO, who threatens legal action and cessation of severance benefits if he does not sign a more restrictive confidentiality agreement. Wigand angrily leaves, and accuses Bergman of betraying him.
Bergman visits Wigand's home and vigorously defends himself. Wigand is reassured but hesitant to reveal anything that might threaten his family's medical coverage, apparently possessing very damaging information.
The Wigand family move into a more modest house, Wigand now working as a teacher. One night his younger daughter Barbara sees someone outside. Wigand finds a fresh footprint in the garden, and receives a sinister phone call.
Knowing that Wigand's confidentiality agreement obstructs any potential story, Bergman contacts Richard Scruggs (Feore), an attorney representing the State of Mississippi in a lawsuit against the tobacco industry, believing that Wigand could be shielded from legal sanction if he were compelled to break confidentiality and testify. Scruggs expresses interest.
Some time later Wigand receives an emailed death threat against him and his family, and finds a bullet in his mailbox. He contacts the FBI, but the agents who attend are hostile, confiscating his computer. Wigand, furious over the threats, demands Bergman arrange an interview.
In the interview, Wigand states that B&W intentionally make their cigarettes more addictive, and that he was fired after refusing to support this. Bergman later arranges a security detail for Wigand's home, and the Wigands suffer marital stress.
Wigand is served with a Kentucky court order prohibiting his testimony in Mississippi, but eventually decides to testify anyway, over the objections of B&W attorneys. On returning to Louisville, Wigand discovers that Liane has left him and taken their daughters.
Bergman, Wallace and Don Hewitt (Hall), the creator and executive producer of 60 Minutes, meet with CBS News' legal counsel, Helen Caperelli (Gershon). Caperelli invokes and describes a legal theory, tortious interference, whereby one who induces someone to break a legal agreement may be sued for "interfering." By this theory, CBS exposes itself to legal action from B&W if Wigand breaks confidentiality in his interview.
Eric Kluster (Tobolowsky), the president of CBS News, decides to omit Wigand's interview from the segment. Bergman objects, believing that CBS Corporate wishes to avoid jeopardizing the pending sale of CBS to Westinghouse, which would enrich both Caperelli and Kluster. Wigand is appalled, and terminates contact with Bergman.
An investigator probes Wigand's personal history, their findings published and circulated to the news media as a 500-page dossier. Bergman learns that The Wall Street Journal will soon use this in a piece questioning Wigand's credibility. Bergman believes that Wigand is being smeared, and arranges for Jack Palladino (playing himself), an attorney and investigator, to evaluate it. The editor of the Journal agrees to delay his story while his reporters examine Palladino's findings.
Infighting at CBS News about the segment prompts Hewitt to order Bergman to take an immediate "vacation." During this, the abridged 60 Minutes segment airs. Bergman, with difficulty, completes a call to Wigand, who is both dejected and furious, accusing Bergman of manipulating him. Bergman defends his own motives and praises Wigand and his testimony.
Bergman is urged by Scruggs to air the full segment, their own lawsuit under threat by a lawsuit from the governor of Mississippi. Bergman is powerless to help, and privately questions his own motives in pursuing the story.
Bergman contacts an editor at The New York Times, disclosing the full story and events at CBS. The Times prints the story on the front page, and condemns CBS in a scathing editorial. The Journal dismisses the dossier as character assassination, and prints Wigand's deposition in full. Hewitt accuses Bergman of betraying CBS, but finds that Wallace now agrees that surrendering to corporate pressure was a mistake.
60 Minutes finally airs the original segment, including the full interview with Wigand. Bergman tells Wallace that he has resigned, believing 60 Minutes' credibility and integrity is now permanently tarnished.
The film ends with text cards summarizing the Tobacco Master Settlement Agreement, and the careers of Wigand and Bergman after the events of the film.

Question: Why does Wigand leave angrily and accuse Bergman of betraying him?
Answer: He is threatened with a  lawsuit and loss of his benefits if he doesn't sign a stricter confidentiality agreement