Campanella began playing semiprofessional baseball on the Philadelphia sandlots when he was 13, and at 15 he was signed to play in the Negro leagues (Negro league). (Campanella's father was of Italian descent, and his mother was African American.) Campanella's skills garnered the attention of Brooklyn Dodgers (Los Angeles Dodgers) general manager Branch Rickey (Rickey, Branch). Attempting to integrate major league baseball, Rickey signed players such as Jackie Robinson (Robinson, Jackie), Don Newcombe, and Campanella to the Dodgers franchise, and in 1946 Campanella began playing for a Dodgers farm team in Nashua, New Hampshire. Campanella moved up to the majors in 1948 and thereby became one of the first black players to break baseball's colour bar. He was the regular catcher for the Dodgers from 1949 until an automobile accident after the 1957 season left him paralyzed.

During his playing career he was named the National League's Most Valuable Player three times (1951, 1953, and 1955) and was recognized as the best fielding catcher in the league in the 1950s. He was also known for his hitting and in 1953 led the league in runs batted in (142) and hit 41 home runs. He played in five World Series (1949, 1952–53, and 1955–56). His autobiography, It's Good to Be Alive, was published in 1959. He was elected to the Baseball Hall of Fame in 1969.