Defense attorney Kevin Lomax (Keanu Reeves) is defending a schoolteacher, Mr. Gettys (Chris Bauer), against a charge of child molestation in the small town of Gainesville, Florida. During the trial, Kevin believes his client is guilty. During a recess, a reporter speaks to Kevin briefly in the restroom and tells Kevin that "nobody wins 'em all." Kevin still decides to go forward and wins the case after a harsh cross-examination of the young witness (Heather Matarazzo) that destroys her credibility.
At a celebration after the conclusion of the trial, Kevin is approached by a representative of the law firm of Milton, Chadwick & Waters, who offers him a large sum of money to help the firm with a trial. Kevin accepts the offer and he and his wife, Mary Ann (Charlize Theron), depart for New York. After successfully performing the task, and because of his good track record of having never lost a case, he is made an offer by John Milton (Al Pacino) to join the firm, for a large salary and a swank apartment. Kevin accepts.
Kevin's first trial is defending a man who ritualistically sacrifices an animal. He soon wins this case, citing Kashrut laws and claiming that the defendant was exercising his rights to freedom of religion. During the trial however, Kevin has begun to spend much time at work and less time with Mary Ann. She feels out of place and abandoned.
Kevin's next assignment is defending Alexander Cullen (Craig T. Nelson) in a high-profile murder trial. This trial is even more demanding of Kevin's time, making him separate more from Mary Ann. He is also having fantasies about Christabella Andreoli (Connie Nielsen), a beautiful co-worker. The alienation between Kevin and Mary Ann is further compounded when Milton tempts Kevin with various vices. Mary Ann starts to show signs of a serious mental illness. Milton suggests that Kevin step down from the trial to look after his wife, saying that "the world would understand", but Kevin decides to go forward.
Eddie Barzoon (Jeffrey Jones), a managing attorney, thinks that Kevin is competing for his job after finding Kevin's name in the company papers as a partner. Kevin claims that he does not know anything about it but Eddie is not mollified and leaves Kevin while threatening to tell a certain person named Weaver about things. Kevin approaches Milton and tells him about the situation with Eddie. While jogging in Central Park, Eddie is beaten to death by two vagrants, who take on demonic appearances during the murder. Mary Ann sees this from her apartment window, causing her mental state to become even worse.
While preparing Cullen's assistant, Melissa Black (Laura Harrington) for a testimony, Kevin believes that she is lying and tells Milton he believes Cullen is guilty. Milton again offers Kevin the opportunity to step down from the trial, saying that he will back him on any decision. Again, Kevin decides to proceed and wins the case.
Upon returning home from the trial Kevin finds Mary Ann in a nearby church. She claims she spent the whole afternoon having sex during which she is maimed by Milton. However, as Kevin had seen Milton in court with him at the time of the alleged attack, he believes Mary Ann has done the damage to herself and has her committed to a mental institution.
Kevin is approached by a man presenting himself as Mitch Weaver. Weaver is an investigator for the Justice Department with insight into shady involvements of the law firm. Kevin doesn't want to listen and tries to walk away, stopping only when Weaver tells him that his former client, Mr. Gettys, was found with the dead body of a young girl. Weaver, however, thinking he has gotten Kevin to listen, walks out in the street, is hit by a car and is killed instantly.
The sequence with Kevin and Mitch Weaver is interwoven with a sequence showing Milton standing at the back of the church where the funeral service for Eddie Barzoon is being held. Milton looks up, grinning, while holding his finger above the stoup of holy water. At the climax of the sequence, he actually dips his finger into the holy water and it boils.
Kevin's mother (Judith Ivey) and Pam (Debra Monk), Kevin's co-worker at the firm, go to visit Mary Ann in the hospital. While being left alone with Mary Ann, Pam appears as a demon to Mary Ann through a mirror. Mary Ann suffers a severe panic attack, locks herself into the room and commits suicide, while Kevin makes an attempt to stop her. After this Kevin learns from his mother that Milton is his father. Devastated and distraught, he leaves the hospital to confront Milton.
Kevin finds Milton in his apartment and Milton admits to having raped Mary Ann. Kevin furiously shoots at Milton with a gun but the bullets do no damage. Kevin learns that Milton is not only his father, but also Satan. Kevin blames Milton for everything that happened but comes to realize it was all his own doing. Kevin finally relents and agrees with Milton, acknowledging that he wanted to win, no matter what, and left Mary Ann behind.
Milton reveals his goal of wanting to beat God and also dismisses the Biblical prophecy saying he's going to lose. He then explains that he wants Kevin and Christabella, now revealed to be Kevin's half-sister, to conceive a child: the Antichrist. Kevin recognizes that this is something he must do out of free will and negotiates with Milton, who offers Kevin anything that he wants. However, Kevin rejects his Satanic heritage and, citing free will, he commits suicide, ending Milton's plans.
We find Kevin in the past, at the recess of the Gettys trial. Upon returning to the trial, Kevin this time announces that he can no longer represent his client, despite the possibility of being disbarred.
The reporter follows Kevin and Mary Ann leaving the courthouse, offering to interview Kevin about his decision, saying it will make him a star. After some prodding from Mary Ann, Kevin accepts the offer. After Kevin and Mary Ann exit the courthouse, the reporter transforms into Milton and says with a grin, "Vanity...definitely my favorite sin"
