Futrelle, who was born in Pike County, Georgia, worked for the Atlanta Journal, where he began their sports section; the New York Herald; the Boston Post; and the Boston American, where, in 1905, his Thinking Machine character first appeared in a serialized version of "The Problem of Cell 13". In 1895, he married fellow writer Lily May Peel, with whom he had two children, Virginia and Jacques "John" Jr.

Futrelle left the Boston American in 1906 to focus his attention on writing novels. He had a house built in Scituate, Massachusetts, which he called "Stepping Stones", and spent most of his time there until his death in 1912.

Returning from Europe aboard the RMS Titanic, Futrelle, a first-cabin passenger, refused to board a lifeboat insisting his wife board instead until the point of forcing her in. His wife remembered the last she saw of him, he was smoking a cigarette with John J. Astor. He perished in the Atlantic. Futrelle's last work, "My Lady's Garter", was published posthumously later in 1912. His wife inscribed in the book, "To the heroes of the Titanic, I dedicate this my husband's book" under a photo of her late husband. On 29 July 1912 his mother, Linnie Futrelle, died in her Georgia home; her death was attributed to grief over her son's death.

Futrelle is used as the protagonist in The Titanic Murders, a novel about two murders aboard the Titanic, by Max Allan Collins.

Novels

• The Chase of the Golden Plate (1906)
• The Simple Case of Susan (1908)
• The Diamond Master (1909 - later adapted into the film serials The Diamond Queen and The Diamond Master)
• Elusive Isabel (1909)
• The High Hand (1911)
• My Lady's Garter (1912)
• Blind Man's Bluff (1914)

Short story collections

• The Thinking Machine (1907), reprinted as The Problem of Cell 13 (1918)
• The Flaming Phantom
• The Great Auto Mystery
• The Man Who Was Lost
• The Mystery of a Studio
• The Problem of Cell 13
• The Ralston Bank Burglary
• The Scarlet Thread
• The Thinking Machine on the Case (1908), UK title The Professor on the Case

Stories

• "The Problem of Cell 13" (1905)
• "The House That Was" (a literary experiment with his wife, in the which The Thinking Machine provided a rational solution to the seemingly impossible and supernatural events of a ghost story written by May)
• "The Phantom Motor"
• Various other short stories (see Augustus S. F. X. Van Dusen for more)

• Donald E. Wilkes, Jr., Georgians on the Titanic & On the Titanic: Jacques Futrelle & May Futrelle Survived Titanic (1994).

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