While in college, Thurber was a writer and cartoonist for his fraternity's student newspaper, the Ohio State Lantern. He also wrote for the monthly literary and humor magazine, the Sundial, and joined the local drama club. Thurber stayed at work for the Sundial for several years until in February 1927, Thurber was hired as a staff writer at The New Yorker. He wrote many short articles and drew dozens of cartoons for the magazine over a period of several years. Thurber also wrote many books during his lifetime, including his famous The Secret Life of Walter Mitty.

In January 1960, a revue of over a dozen of Thurber's classic works was created, entitled A Thurber Carnival. The production included dramatizations of The Secret Life of Walter Mitty, Mr. Prebel Gets Rid of His Wife, The Pet Department, If Grant Had Been Drinking at Appomattox, The Macbeth Murder Mystery, Casuals of the Keys, File and Forget, The Unicorn in the Garden, The Little Girl and the Wolf, The Wolf at the Door, and Gentlemen Shoppers, a new piece Thurber wrote for the show; a recitation of The Night the Bed Fell; a slide presentation of The Last Flower; and Word Dance, featuring versions of the captions from some of Thurber's old cartoon, recited by twirling actors.

On the morning of October 4th, 1961, Thurber collapsed on his way to the bathroom. His wife Helen found him lying in a puddle of blood and quickly summoned an ambulance. He was taken to Doctors Hospital and was diagnosed with either a cerebral hemorrhage or a brain tumor. He underwent surgery immediately, and a tumor was removed from near the speech-control center of Thurber's brain. He lapsed into a coma and contracted pneumonia and developed a blood clot in his lung. On the afternoon of November 2nd, 1961, Thurber's wife Helen received a call from the hospital telling her that her husband was fading fast. By the time she arrived at his bedside, he was gone.

James Thurber's ashes were buried at Columbus's Green Lawn Cemetery with his family on November 8, 1961. He leaves behind a diverse and wonderful potpourri of drawings, magazine articles, books, plays, and other works, which have all become a part of modern-day American humor. Neither Thurber nor his incredible achievements are to be forgotten.