Howard Roark, a young architecture student, is expelled from the Stanton Institute of Technology for refusing to abide by its outdated traditions. Despite an effort by some professors to defend Roark and a subsequent offer to continue at Stanton from the dean, Roark chooses to leave the school. He goes to New York City to work for Henry Cameron, a disgraced architect whom Roark admires. Cameron, who once was architecture’s modernist hero, has fallen from fame due to the fickle demands of society and his own caustic personality. His work serves as an inspiration for Roark. Roark’s highly successful but vacuous schoolmate, Peter Keating, also moves to New York to work for the prestigious architectural firm, Francon & Heyer. Roark and Cameron create inspired work, but their projects rarely receive recognition, whereas Keating’s ability to flatter and please brings him almost instant success despite his lack of originality.
After leaving Cameron’s employ, Roark briefly opens his own practice, but he has trouble finding clients and eventually closes his office rather than compromise his ideals to win business from clients who want more conventional buildings. He takes a job at a Connecticut granite quarry owned by Guy Francon of Francon & Heyer. Meanwhile, Keating has developed an interest in Francon’s beautiful, temperamental and idealistic daughter, Dominique, who works as a columnist for The New York Banner, a yellow press-style newspaper. While Roark is working in the quarry, he encounters Dominique, who has retreated to her family’s estate in the same town as the quarry. There is an immediate attraction between them. Rather than indulge in traditional flirtation, the two engage in a battle of wills that culminates in a rough sexual encounter that Dominique describes later in the story as "rape". Shortly after their encounter, Roark is notified that a client is ready for him to start on a new building, and he leaves without Dominique even knowing his name.
Ellsworth Toohey, author of the popular architecture column One Small Voice in the Banner, is an outspoken socialist, who is covertly rising to power by shaping public opinion through his column and his circle of influential associates. Toohey sets out to destroy Roark through a smear campaign he spearheads. As the first step, Toohey convinces a weak-minded businessman named Hopton Stoddard to hire Roark as the designer for a temple dedicated to the human spirit and gives Roark carte blanche to design it as he sees fit. Roark designs the temple, including a naked statue of Dominique, which creates a public outcry. Toohey manipulates Stoddard into suing Roark for general incompetence and fraud. At Roark’s trial, every prominent architect in New York (including Keating) testifies that Roark’s style is unorthodox and illegitimate. Dominique defends Roark, but Stoddard wins the case and Roark loses his business again.
Dominique believes that greatness such as Roark’s should never be offered to a public unable to appreciate it, and decides that since she cannot have the world she wants (in which men like him are recognized for what they are) she will live completely and entirely in the world she has, which shuns him and praises Keating. That evening, Dominique pays Keating a visit, and makes him a one-time offer of her hand in marriage. Keating accepts, though he is engaged to Toohey’s niece Catherine, and they are married that evening. Dominique turns her entire spirit over to Keating, hosting the dinners he wants, agreeing with him, and saying whatever he wants her to say. She fights Roark, and persuades his potential clients to hire Keating instead. Despite this, Roark continues to attract a small but steady stream of clients who see the value in his work.
To win Keating a prestigious architecture commission offered by Gail Wynand, the owner and editor-in-chief of the Banner, Dominique agrees to sleep with Wynand. Wynand then buys Keating’s silence and his divorce from Dominique, after which Wynand and Dominique are married. Wynand subsequently discovers that every building he likes is done by Roark, so he enlists Roark to build a home for himself and Dominique. The home is built, and Roark and Wynand become great friends, although he does not know about Roark’s past relationship with Dominique.
Now washed up and out of the public eye, Keating realizes he is a failure. Rather than accept retirement, he pleads with Toohey for his influence to get the commission for the much sought after Cortlandt housing project. Keating knows that his most successful projects were aided by Roark, so he asks for Roark’s help in designing Cortlandt. Roark agrees to design it in exchange for complete anonymity—and the agreement that it would be built exactly as he designed.
When Roark returns from a long yacht trip with Wynand he finds that, despite the agreement, the Cortlandt Homes project has been changed. Roark asks Dominique to distract the night watchman and dynamites the building to prevent the subversion of his vision. The entire country condemns Roark, but Wynand finally finds the courage to follow his convictions and orders his newspapers to defend him. The Banner’s circulation drops and the workers go on strike, but Wynand keeps printing with Dominique’s help. Wynand is eventually faced with the choice of closing the paper or reversing his stance and agreeing to the union demands. He gives in; the newspaper publishes a denunciation of Roark over Wynand’s signature.
At the trial, Roark seems doomed, but he rouses the courtroom with a speech about the value of ego and the need to remain true to oneself. The jury finds him not guilty. Roark finally wins Dominique. Wynand, who has finally grasped the nature of the "power" he thought he held, asks Roark to design one last building, a skyscraper that will testify to the supremacy of man: "Build it as a monument to that spirit which is yours...and could have been mine." A brief epilogue eighteen months later shows the Wynand Building well on its way to completion. The last scene follows Dominique (now Mrs. Roark), entering the site to meet Roark atop the steel framework.