He began his professional career with the Birmingham Black Barons of the Negro National League in 1947. The New York Giants, who had purchased his contract in 1950, called him up to the major leagues in 1951, upon which he won the Rookie of the Year Award. He then served in the U.S. Army in the Korean War, missing part of the 1952 season and all of the 1953 season. He returned to the Giants in 1954, winning the National League Most Valuable Player Award and leading them to a World Series victory, a four-game sweep of the Cleveland Indians. Mays is remembered for making one of the greatest defensive plays of all time in Game 1 of the series, an over-the-shoulder catch off a long drive to deep center field by Vic Wertz.
Mays moved along with the Giants to San Francisco for the 1958 season. The Giants made the World Series in 1962, only to lose to the New York Yankees in seven games. Mays won his second of two Most Valuable Player Awards in 1965. He continued to play with that franchise until partway through the 1972 season, when he joined the New York Mets. He played with them until his retirement after the 1973 season. The Mets made the World Series in Mays' final year, only to lose in seven games to the Oakland Athletics.
Mays is the godfather of baseball star Barry Bonds.