A woman is arrested for murder, but a celebrated detective suspects the overwhelming evidence is a deliberate misdirection. Roger Sheringham, a novelist with a penchant for solving crimes, believes Mrs. Bentley is innocent despite the arsenic found in her husband's medicine, food, and drink, which has led to a media frenzy and even her lawyers' belief in her guilt. He must navigate the constraints of a legal system focused on the apparent facts and the public's conviction, all while uncovering the psychological underpinnings of the crime. The narrative framework appears to be a traditional third-person detective story, focusing on Sheringham's deductive process.

The Wychford Poisoning Case is recognized as a seminal work in the mystery genre, often cited as the first psychological crime novel. Its innovative approach to character and motive, predating many later explorations of the mind in detective fiction, has cemented its place in the Golden Age canon. The novel's enduring influence is noted, particularly for its contribution to the development of the genre's psychological depth. The return of Roger Sheringham also highlights its significance within the broader context of classic detective fiction.