Santo, who had battled diabetes throughout his life, died on Thursday night in Arizona from bladder cancer, the baseball club said.
During a stellar 15-year career, all but one with the Cubs, Santo batted .277 with 342 home runs and 1,331 RBI. He won five Gold Glove awards as a third baseman, and the Cubs retired his uniform number 10 in 2003.
Santo tearfully accepted the accolade from his team, but was disappointed several times in not being voted into baseball's Hall of Fame.
He served as the club's radio announcer even after losing both legs to diabetes, which was diagnosed when he was age 18. He kept the diabetes secret during his playing career.
He was a member of the board of directors of the Juvenile Diabetes Foundation. The Ron Santo walkathon has raised more than $40 million since its inception in 1979.
(Reporting by Andrew Stern; Editing by Greg McCune).