Foote was born and raised in Greenville, Mississippi. His ancestor, Richard Foote, came in 1688 from London to Chotank in King George County, Virginia to represent his father's interest in settlement of the Brenttown tract.
Shelby attended the University of North Carolina before entering the United States Army in 1940. He was commissioned a captain of artillery, but lost his commission and was dismissed from the Army in 1944 for using a government vehicle, against regulations, to visit a girlfriend (who later would become his first wife). He later enlisted in the United States Marine Corps, but did not see combat duty.
After being discharged from the military, Foote was briefly a journalist. However, he began writing historical fiction, mostly set in the period surrounding the American Civil War. Among his works are Follow Me Down (1950), Love in a Dry Season (1951), and Shiloh (1952). Although he was not one of America's best-known fiction writers, Foote was admired by his peers - among them his lifelong friend Walker Percy.
Although he never completed college or received formal training as a historian, Foote's ability to create a realistic portrayal of the American Civil War - factually accurate, richly detailed, and entering into the minds of men on both sides - led his editors at Random House to invite him to write a short history of the war to appear for the conflict's centennial.
Foote subsequently wrote a comprehensive three volume, 3000-page history of the American Civil War, together entitled The Civil War: A Narrative, which is considered by many to be a classic. The individual volumes include Fort Sumter to Perryville (1958), Fredericksburg to Meridian (1963), and Red River to Appomattox (1974).
Foote appeared in Ken Burns' PBS documentary The Civil War. Foote's drawl, erudition, and quirk of speaking as if the war were still going on, made him a favorite. The exposure made him a minor celebrity (a role he did not relish, especially as increased public attention gave him less time to work on his novels), and generated renewed popular interest in his books.
Despite his Southern upbringing, Foote deliberately avoided Lost Cause mythologizing in his work. He considered Abraham Lincoln and Nathan Bedford Forrest to be the only two authentic geniuses of the war, a belief that raised the ire of Forrests' granddaughter. He also believed that the cause of the South was lost from the minute they declared war.
Foote was a Guggenheim Fellow three times, and served as a lecturer at the University of Virginia and the University of Memphis.
From the 1950s until his death, he lived in Memphis, Tennessee. In 1987, he became a charter member of the Fellowship of Southern Writers at the University of Tennessee at Chattanooga. In one of his last television projects, Foote graciously consented to narrate the 1990's Television Trilogy, The 1840 Carolina Village, produced by award-winning PBS and Travel Channel producer C. Vincent Shortt. "Working with Shelby was a genuinely illuminating and humbling experience", said Shortt. "He was the kind of academician who could weave a Civil War story into a discussion about fried green tomatoes -- and do so without an ounce of presumption or arrogance. He was a treasure."
In the early 1990s, Foote was interviewed by journalist Tony Horwitz for the project on American memory of the Civil War which Horwitz eventually published as Confederates In The Attic (1994).
Foote died at his home on June 27, 2005. He is buried in Elmwood Cemetery in Memphis, Tennessee.
