In Elmer Gantry, Sinclair Lewis uses the character of Elmer Gantry to represent, without nuance or ambiguity, what he viewed as the prototypical evangelical minister of his day: ambitious and charismatic; driven by his lust for women, money, and power; and completely unrepentant in his scorn for those who believe in the faith he deceptively proclaims. At the novel’s beginning, Gantry is captain of the football team at the rowdy campus at Terwillinger College, a Baptist school. Gantry’s mother is a strict fundamentalist, so Gantry spent much of his childhood in church, where he learned the dour lifestyle of a Christian. Now in college, Gantry and his roommate, Jim Lefferts, spend much of their time drinking and chasing women, but their primary amusement comes from ridiculing their classmates’ incessant religious proselytizing. When a charismatic preacher comes to town for a revival meeting, he seeks out Gantry and tricks him into attending. With Jim (who is more skeptical and quick-witted than Gantry) home sick in bed, Gantry attends the meeting with his mother and is converted. Gantry’s conversion makes him the talk of the campus, and Jim soon moves out. After several failed efforts to hear God calling him to the ministry, Gantry shares a bottle of whiskey with Jim and emerges with the feeling of having received the call.

He goes to Mizpah Seminary, where he entertains his classmates with tales of his sexual escapades. The dean sends Gantry and classmate Frank Shallard to pastor a nearby church. There they meet their host, Deacon Bains, and his daughter Lulu, an ingenue whom Gantry continually tries to seduce. Gantry is bored by school, but Shallard is drawn to a professor who eventually confesses his atheism to Shallard. After exposing the professor’s secret, Gantry receives an anonymous gift of thirty dimes, which he uses to buy photographs of strippers. Gantry considers Shallard’s company an obstacle to his plans with Lulu, so he engineers Shallard’s resignation with accusations of apostasy. When Deacon Bains discovers Gantry’s affair with Lulu and forces him to propose, Gantry tricks another man into an entanglement with Lulu and is released from the engagement. On the trip to his new church, he gets drunk and carouses with women; he is discovered and is dismissed from the seminary.

After two years as a traveling salesman, Gantry attends a revival meeting and is immediately bewitched by the evangelist Sharon Falconer. He is soon invited to preach at one of her meetings. He confesses his love for her and they begin an affair, peppering their lovemaking with religious imagery. Gantry introduces savvy business practices to Sharon’s ministry and manipulative psychology to the services themselves, and Sharon becomes wealthy as a result. When she overhears Gantry seducing their pianist, she fires them, but Gantry convinces her to reconsider. At their next revival, the tent catches fire and kills a hundred people, including Sharon, but Gantry climbs over trapped women and escapes.

He joins the staff of a metaphysical cult but is fired when he is caught stealing from the collection plate. He seeks out Shallard, who has largely given up his faith but has been persuaded by a Methodist pastor to continue in the ministry and is now at a church in Zenith. There, Gantry befriends the Methodist bishop and is appointed pastor of a church in Banjo Crossing. He charms the congregation and quickly becomes part of the community. Before long, he marries Cleo Benham, the choir director, but finds her an unenthusiastic lover. Over the next few years, he is appointed to larger and larger parishes, eventually to a church in Zenith.

Gantry befriends a famous criminal attorney, T. J. Rigg, who becomes his adviser and confidant. Gantry maintains friendships with most pastors in Zenith but loathes Philip McGarry, a pastor in a poor neighborhood who has been a friend and mentor to Shallard. Gantry’s pugnacious sermons quickly make him popular in Zenith, but the workload soon overwhelms him and alienates him from Cleo. One Sunday, he is surprised to see Lulu in church, and the next day he begins an affair with her. He befriends local reporters in hopes of getting his name in the papers, and eventually he leads a raid on Zenith’s red-light district. Once Gantry accuses the city government of protecting the brothels and drug dealers, he becomes one of the most powerful men in Zenith. McGarry accidentally reveals Shallard’s doubts to Gantry, so Gantry uses them to defame Shallard as part of a campaign to raise money for a new church building. Shallard attempts to stand against Gantry’s attempts to destroy him, but eventually he resigns from his pulpit. Later, he is kidnapped and beaten nearly to death, an episode that leaves him blinded. Gantry threatens to avenge him but takes no action.

Gantry’s fame continues to grow, and he is soon preaching at churches across America. He hires a new secretary, Hettie Dowler, who replaces Lulu as his mistress. One night, Hettie’s husband catches them together; blackmail threats follow, and Gantry realizes that Hettie is part of the plot. The affair threatens to destroy Gantry, but Rigg hires a detective to besmear Hettie, and she and her husband are forced to sign an affidavit declaring Gantry’s innocence. Later, in the middle of a church service, Gantry realizes that he misses Hettie but quickly spots a new choir member whom he hopes to get to know better.