Thurber were born in Columbus, Ohio. He attended The Ohio State University, where he was a member of Phi Kappa Psi Fraternity. He joined the staff of The New Yorker in 1927 and continued to contribute to the magazine through the 1950s.

Thurber was married twice. His only child, Rosemary, was born during his first marriage to Althea Adams, from 1922 to 1935. His second marriage, to Helen Wismer in 1935, endured until his death.

Due to a childhood injury, Thurber lost one eye. He progressively suffered from very poor eyesight in his remaining eye. His sight grew weaker as he grew older. He also suffered from a toxic-thyroid condition for more than 2 years in the 1950's, and died of complications from the removal of a benign brain tumor.

Thurber worked hard in the 1920's, both in the U.S.A. and in France, to establish himself as a professional writer. However, unique among major American literary figures, he became equally well known for his simple, surrealistic drawings and cartoons. Both his skills were helped along by the support of, and collaboration with, fellow New Yorker staff member E. B. White. White insisted that Thurber's sketches could stand on their own as artistic expressions--and Thurber would go on to draw six covers and numerous classic illustrations for the New Yorker.

While able to sketch out his cartoons in the usual fashion in the 1920's and 1930's, his failing eyesight later required him to draw them on very large sheets of paper using a thick black crayon (also, on black paper using white chalk, from which they were photographed and the colors reversed for publication). Regardless of method, his cartoons became as notable as his writings; they possessed an eerie, wobbly feel that seems to mirror Thurber's idiosyncratic view on life. (Dorothy Parker, contemporary and friend of Thurber, referred to his cartoons as having the "semblance of unbaked cookies.")

Many of his short stories are humorous fictional memoirs from his life, but he also wrote darker material. "The Dog Who Bit People" and "The Night the Bed Fell" are among his best short stories; they can be found in My Life and Hard Times, the creative mix of autobiography and fiction which was his 'break-out' book. Also notable, and often anthologized, are "The Secret Life of Walter Mitty", "The Catbird Seat," "The Greatest Man in the World" and "If Grant Had Been Drinking at Appomatox", which can be found in The Thurber Carnival.

Thurber teamed with college schoolmate (and actor/director) Elliot Nugent to write a major Broadway hit comic drama of the late 1930's, "The Male Animal" (made into a film in 1942, starring Henry Fonda, Olivia de Haviland, and Jack Carson.). Near the end of his life, Thurber finally was able to fulfill his long-standing desire to be on the professional stage by playing himself in a few performances of the anthology "A Thurber Carnival," made up of various acted-out stories and cartoon captions. Thurber won a special Tony Award for the adapted script of the "Carnival."

A network television show based on Thurber's writings and life entitled My World and Welcome to It was broadcast from 1969 to 1970, starring William Windom as the Thurber figure. Windom went on to perform Thurber's work in his one-man stage performances. The animation of his cartoons on this show led to the 1972 Jack Lemmon film "The War Between Men And Women," which concludes with a fine animated rendering of Thurber's classic anti-war work "The Last Flower."