Thurber was born in Columbus, Ohio to Charles L. Thurber and Mary Agnes (Mame) Fisher Thurber. Both of his parents greatly influenced his work. His father, a sporadically employed clerk and minor politician who dreamed of being a lawyer or an actor, is said to have been the inspiration for the small, timid protagonist typical of many of his stories. Thurber described his mother as a born comedienne and one of the finest comic talents I think I have ever known. She was a practical joker, on one occasion pretending to be crippled and attending a faith healer revival, only to jump up and proclaim herself healed.

Thurber had two brothers, William and Robert. Once, while playing a game of William Tell, his brother William shot James in the eye with an arrow. Because of the lack of medical technology, Thurber lost his eye. This injury would later cause him to be almost entirely blind. During his childhood he was unable to participate in sports and activities because of his injury, and instead developed a creative imagination, which he shared in his writings.

From 1913 to 1918, Thurber attended The Ohio State University, where he was a member of the Phi Kappa Psi Fraternity. He never graduated from the University because his poor eyesight prevented him from taking a mandatory ROTC course. In 1995 he was posthumously awarded a degree.

From 1918 to 1920, at the close of World War I, Thurber worked as a code clerk for the Department of State, first in Washington, D.C. and then at the American Embassy in Paris, France. After this Thurber returned to Columbus, where he began his writing career as a reporter for the Columbus Dispatch from 1921 to 1924. During part of this time, he reviewed current books, films, and plays in a weekly column called Credos and Curios, a title that later would be given to a posthumous collection of his work. Thurber also returned to Paris in this period, where he wrote for the Chicago Tribune and other newspapers.

In 1925