Richard Lee Rhodes was born on July 4, 1937 at Kansas City, Kansas, the youngest of three sons born to Arthur and Georgia Collier Rhodes. Following his mother's suicide in 1938 and his father's subsequent remarriage, Rhodes and his brother Stanley suffered severe childhood abuse, which culminated in their admittance to the Andrew Drumm Institute for orphaned boys at Independence, Missouri.

In 1959, Rhodes graduated cum laude from Yale University, earning a bachelor's degree in history and letters. He afterward trained as a writer at Newsweek magazine, taught English, and worked in corporate public relations before turning full-time to writing.

Rhodes has published many books, both fiction and non-fiction, as well as articles in numerous fields of interest. His 1986 history of the atomic bomb's development, The Making of the Bomb, was awarded the 1988 Pulitzer Prize in Non-Fiction, as well as a National Book Award and a National Book Critics Circle Award. Topics of Rhodes's other major works have included the American Middle West, the Ozarks, the 19th century artist and naturalist John James Audubon, the development of the hydrogen bomb, the history of "mad cow" and other similar diseases, the history of Adolf Hitler's death squad, the life of criminologist Lonnie Athens, case histories of childhood abuse, and the ill-fated settlers of the Donner Party.

Rhodes is an affiliate of Stanford University's Center for International Security and Cooperation and has received grants from the Ford Foundation, the Guggenheim Foundation, the MacArthur Foundation, and the Alfred P. Sloan Foundation.