The first baseman, who also had stints with the San Diego Padres as well as the New York Yankees, spent a decade with the Cubs, winning the World Series with the side in 2016 - their first since 1908.
Rizzo, a fan favourite wherever he went, had 1,644 hits and 303 home runs during his big league career, as well as appearing in three All-Star games. He also won three Gold Glove awards at first base, an accolade given to the best fielder in their position every season.
He will return to the Cubs' home of Wrigley Field on Saturday to throw out the first pitch before their game against the Tampa Bay Rays and officially retire from the game. The 36-year-old will then become an official ambassador for the side.
In a statement, the Cubs' executive chairman, Tom Ricketts, said of Rizzo: "His play on the field spoke for itself and was recognised with multiple All-Star appearances, Gold Glove awards, the Roberto Clemente Award, and, ultimately, being a team leader on the 2016 World Championship winning team."
Drafted by the Boston Red Sox in 2007, Rizzo spent his rookie campaign with the Padres before joining the Cubs. After 10 years in Illinois, he was traded to the Yankees in 2021, where he would make another World Series, losing to the Los Angeles Dodgers last autumn.
Rizzo also battled illness during his career, staving off a cancer diagnosis in 2007 before setting up the Anthony Rizzo Foundation to support children with cancer.