A paleontologist at Columbia University, the American Museum of Natural History, and Harvard University's Museum of Comparative Zoology, Simpson was among the first to apply quantitative methods to the study of rates of evolution as gleaned from the fossil record of mammals. His 1944 book, "Tempo and Mode of Evolution," is one of cornerstones of the the Modern Synthesis, He interpreted his data to show that evolution proceeds in a slow tempo and gradual mode, as advocated by Darwin.

Simpson served in the US Army during World War II. As a junior officer in George Patton's Third Army, Simpson got into trouble over his refusal to shave off his beard.