Born in Mart, Texas, Thomas often shadowed his father who was a general practice Doctor. Later, he attended the University of Texas at Austin where he studied chemistry and chemical engineering, graduating with a B.A. in 1941 and an M. A. in 1943. While Thomas was an undergraduate he met his wife, Dorothy (Dottie) Martin while she was training to be Journalist. They had three children. Thomas entered Harvard Medical School in 1943, receiving an M.D. in 1946. Dottie became a lab technician during this time to support the family, and the pair worked closely thereafter. He did his residency at Peter Bent Brigham Hospital before joining the US Army. "In 1955, he was appointed physician in chief at the Mary Imogene Bassett Hospital, now Bassett Medical Center, in Cooperstown, N.Y., an affiliate of Columbia University."

At Mary Imogene Bassett, he began to study rodents that received lethal doses of radiation who were then saved by an infusion of marrow cells. At the time, patients who underwent bone marrow transplantation all died from infections or immune reactions that weren't seen in the rodent studies. Thomas began to use dogs as a model system. In 1963, he moved his lab to the United States Public Health Service in Seattle.

Thomas also received National Medal of Science in 1990. In 2003 he was one of 22 Nobel laureates who signed the Humanist Manifesto.