As a 17-year-old in 1954, Mazeroski signed with the Pittsburgh Pirates, a team for which he would play his entire career. Originally signed as a shortstop, he was quickly moved to second base and made his Major League debut on July 7, 1956.

Mazeroski was noted for his defensive prowess and earned his first of eight Gold Glove Awards in 1958. He had a career .983 fielding percentage and led the National League in assists nine times, and holds the major league career record for double plays by a second baseman.

Despite his defensive play often overshadowing his offensive contributions, Mazeroski had several fine offensive seasons. In 1958, he hit .275, hit 19 home runs (a career best) and had 68 RBIs and was considered for the MVP Award. In 1966 he knocked in 82, a career best. During his peak seasons (1957-68), he drove on more runs than any other middle infielder of the period. In the 1960 World Series, Mazeroski hit a game-winning home run off New York Yankees pitcher Ralph Terry which won the series for Pittsburgh. It was the first time a World Series had ever been ended by a home run and will likely remain the defining event of Mazeroski's career. (The feat has been accomplished once since, by Joe Carter in the 1993 World Series.)

Mazeroski was elected into the Baseball Hall of Fame in 2001. In a cameo appearance in The Odd Couple, Mazeroski hit into a game-ending triple play.

Warren Consolidated High School has since joined other schools to form Buckeye Local High School in Rayland, Ohio. Buckeye Local honored him in 2003 naming their new baseball field after him and placing a monument behind home plate, near the road. Quotation