His career began as a copy editor and sportswriter for the Atlanta Constitution. In 1943, he began announcing games for the Atlanta Crackers of the Southern Association. In 1948, Harwell became the only announcer in baseball history to be traded for a player, when the Brooklyn Dodgers General Manager, Branch Rickey traded catcher Cliff Dapper to the Crackers in exchange for breaking Harwell's broadcasting contract.
Harwell also served as the play-by-play man for both the New York Giants and Baltimore Orioles before becoming the Voice of the Detroit Tigers from 1959 to 2002. Harwell is a member of the Baseball Hall of Fame (one of only five broadcasters), the Radio Hall of Fame and the National Sportscasters Hall of Fame, among many others.