Donald Barthelme was born to two students at the University of Pennsylvania. The family moved to Texas two years later, where Barthelme's father would become a professor of architecture at the University of Houston, where Barthelme would later major in journalism. In 1951, still a student, he wrote his first articles for the Houston Post. Barthelme was drafted into the Korean War in 1953, arriving in Korea on July 27, the very day the cease-fire ending the war was signed. He served briefly as the editor of an Army newspaper before returning to the U.S. and his job at the Houston Post. Once back, he continued his studies at the University of Houston, studying philosophy. Although he continued to take classes until 1957, he never received a degree. He spent much of his free time in Houston’s “black” jazz clubs, listening to musical innovators such as Lionel Hampton and Peck Kelly, an experience which influenced his later writing.
Barthelme's relationship with his father was a struggle between a rebellious son and a demanding father. In later years they would have tremendous arguments about the kinds of literature in which Barthelme was interested and wrote. While in many ways his father was avant-garde in art and aesthetics, he did not approve of the post-modern and deconstruction schools. Barthelme's attitude toward his father is delineated in the novels The Dead Father and The King as he is pictured in the characters King Arthur and Lancelot. Barthelme's independence also shows in his moving away from the family's Roman Catholicism (his mother was especially devout), a separation that troubled Barthelme throughout his life as did the distance with his father. He seemed much closer to his mother and agreeable to her strictures.
Barthelme went on to teach for brief periods at Boston University, University at Buffalo, and the College of the City of New York, where he served as Distinguished Visiting Professor from 1974-75. He married four times. His second wife, Helen Barthelme, later wrote a biography entitled Donald Barthelme: The Genesis of a Cool Sound, published in 2001. With his third wife Birgit, a Dane, he had his first child, a daughter named Anne, and near the end of his life he married Marion, with whom he had his second daughter, Kate. Marion and Donald remained wed until his 1989 death from throat cancer. Donald Barthelme's brothers Frederick (1943 - ) and Steven (1947- ) are also respected fiction writers and teachers at The University of Southern Mississippi.