In The Doorbell Rang, eccentric New York detective Nero Wolfe goes up against J. Edgar Hoover's FBI. Mrs. Rachel Bruner has sent a book critical of the FBI to 10,000 important people, and now she's under investigation and wants it to stop. With the lure of a $100,000 retainer, Wolfe sets out to find dirt on the FBI. Instead, he uncovers the murder of Morris Althaus, not by three FBI agents on the scene, but by Althaus's rejected lover. Wolfe tricks the FBI into invading his home, and under threat of disclosure of their illegal acts, he forces the FBI to stop investigating his client.

At the beginning of the novel, Nero Wolfe is approached by Mrs. Bruner, a wealthy widow who wants the FBI to stop investigating her. Because she offers him a hundred-thousand-dollar retainer with no strings attached, Wolfe accepts her impossible-sounding job. He begins by gathering information about recent FBI activity in New York, but he finds little that might be useful. Archie begins his investigations, but he is frustrated at every turn. Then, a mysterious message is delivered to Archie to meet an informant.

The informant turns out to be Inspector Cramer of New York Homicide South, who has an unsolved murder on his hands. Cramer believes that an FBI agent killed Morris Althaus, a writer who was working on a story about the FBI. He turns over the information about the killing to Archie, in hopes that Wolfe can solve the murder. The crime gives Wolfe a dilemma, though, because if he finds out an FBI agent killed Alhaus, it won't give him leverage he can use to stop the FBI from harassing his client. Wolfe and Archie set out to prove instead that someone else murdered Althaus.

Wolfe discovers that one of Althaus's articles sent a man named Frank Odell to prison, and Archie goes to meet him. Archie finds that Odell can be linked back to Mrs. Bruner, and then he discovers that Sarah Dacos, Mrs. Bruner's secretary lives in the apartment below Althaus's and witnessed the FBI agents leaving the scene of the crime. Archie investigates further and finds out that Sarah Dacos and Althaus were lovers. Archie breaks into Sarah Dacos's apartment and finds the gun that killed Althaus.

Meanwhile, Wolfe has decided on a plan to trap the FBI. He hires two actors to impersonate himself and Archie and creates the appearance that he, Archie, and his staff are going to a dinner, leaving the brownstone empty. Meanwhile, Wolfe has smuggled in three more detectives, and he catches two FBI agents red-handed breaking into his house. Wolfe takes their FBI identification and uses it as leverage to get the FBI to stop investigating his client. Then, he turns over the evidence about Sarah Dacos to Inspector Cramer, solving the murder as well as fulfilling the requirements of his job for Mrs. Bruner.