During the 1930s, Welty worked as a publicity agent for the Works Progress Administration, a job that sent her around Mississippi. On her own time, she took some memorable photographs during the Great Depression of people from all economic and social classes. Collections of her photographs were published as One Time, One Place (1971) and Photographs (1989). Her photography was the basis for several of her short stories, including "Why I Live at the PO", which was inspired by a woman she photographed ironing in the back of a small post office.

Welty was focused on her writing but continued to take photographs until the 1950s. Her first short story, "Death of a Traveling Salesman", appeared in 1936. Her work attracted the attention of author Katherine Anne Porter, who became a mentor to Welty and wrote the foreword to Welty's first collection of short stories, A Curtain of Green, in 1941. The book immediately established Welty as one of American literature's leading lights and featured the stories "Why I Live at the P.O.", "Petrified Man", and the frequently anthologized "A Worn Path". Excited by the printing of Welty's works in such publications such as the Atlantic Monthly, the Junior League of Jackson, of which Welty was a member, requested permission from the publishers to reprint some of her works.

Her novel The Optimist's Daughter won the Pulitzer Prize for Fiction in 1973. In 1992, Welty was awarded the Rea Award for the Short Story for her lifetime contributions to the American short story.

Welty was a charter member of the Fellowship of Southern Writers, founded in 1987. She also taught creative writing at colleges and in workshops. She lived near Jackson's Belhaven College and was a common sight among the people of her hometown.

• Eudora, the name given to the Internet email program developed by Steve Dorner in 1990, was inspired by Welty's story "Why I Live at the P.O."

• The state of Mississippi established a "Eudora Welty Day."

• Each October, Mississippi University for Women hosts the "Eudora Welty Writers' Symposium" to promote and celebrate the work of contemporary Southern writers.

• Mississippi State University sculpture professor, Critz Campbell, has designed furniture inspired by Welty that has been featured in the Smithsonian Magazine, New York Times, L.A. Times, Washington Post, Elle Magazine and the Discovery Channel.