Lawrence Blakeley has traveled to Pittsburgh to collect the deposition of rich industrialist John Gilmore, chief witness for the prosecution in a forgery trial, while his legal partner Richey McKnight visits his fiancee at her home in Richmond. What should have been a standard legal procedure to help secure a conviction in their favor becomes instead the beginning of great misfortune for Blakeley.

After being forced to sleep in a vacant bunk upon finding a drunk occupying his paid-for one, Blakeley wakes up to discover that all his belongings are missing. The search for the stolen evidence is further complicated when a lifeless body is discovered, and Blakeley—the murder weapon mysteriously appearing in his possession—becomes the main suspect.

Blakeley has to work out how a tangled web of clues that surrounds the murder, a beautiful but mysterious woman with a familiar face, and a seemingly unrelated legal case are all interconnected to his predicament.

Published in 1909, The Man in Lower Ten was an early pioneer in American crime novels and an instant bestseller, helping to establish passenger trains as suitable settings for murder mysteries.