He was born in Philadelphia, Pennsylvania. His father was of Italian descent; his mother was African American, so he was barred from Major League Baseball until 1947, when players of color were admitted to the major leagues.

Campanella played for the Brooklyn Dodgers (now the Los Angeles Dodgers) from 1948 to 1957, as their regular catcher. In 1948 he had three different uniform numbers (33, 39, and 56) before settling down to number 39 for the rest of his career.

His first game was on April 20, 1948.

He played in the All-Star Game every year from 1949 to 1956.

He received the Most Valuable Player (MVP) award in the National League three times: in 1951, 1953, and 1955. He was in tenth place in the MVP voting in 1952.

In 1953, he hit 40 home runs in games in which he appeared as a catcher, a record that lasted until 1996, when it was broken by Todd Hundley. It's also this feat which earned him a mention in Billy Joel's history themed song "We Didn't Start the Fire".

Campanella was paralyzed from the chest down after an automobile accident in January 1958. Through physical therapy, he eventually was able to gain substantial use of his arms and hands. He was able to feed himself, shake hands, and gesture while speaking, but he would be confined to a wheelchair for the remainder of his life.

In May of 1959, the Dodgers, by then relocated to Los Angeles, honored Campanella with "Roy Campanella Night" at the Los Angeles Memorial Coliseum. The New York Yankees agreed to make a special trip to Los Angeles to play an exhibition game against the Dodgers for the occasion. The attendance at the game was over 93,000, still the largest crowd ever to attend a Major League Baseball game.

In 1969 Roy Campanella was inducted into the Baseball Hall of Fame, the second player of African-American heritage so honored after Jackie Robinson. On June 4, 1972 the Dodgers retired his uniform number 39 alongside Jackie Robinson's (42) and Sandy Koufax's (32).

After his playing career, Campanella remained involved with the Dodgers. In 1978, he moved to California and remained active in the Dodgers' community relations department. He served as a mentor and adviser to young catchers in the Dodger organization.

In 1993, Campanella died at his home in Woodland Hills, California. He was interred in the Forest Lawn, Hollywood Hills Cemetery in Los Angeles.

His widow, Roxie, died in 2004.

In 1999, Campanella ranked number 50 on The Sporting News' list of the 100 Greatest Baseball Players, and was a nominee for the Major League Baseball All-Century Team.

In 2006, Campanella will be featured on a United States postage stamp . The stamp is one of a block of four honoring Baseball Sluggers.