Rizzo went deep to center off Mike Fiers (6-5) in the first. He jogged home to score from third in a two-run sixth on Arismendy Alcantara's double just inside the first base line.
Rizzo became the first Cubs left-handed hitter with 32 homers since Rick Monday in 1976.
Jacob Turner (6-11) allowed four hits and two runs in five-plus innings. He beat Milwaukee for the second time since being traded from Miami in August.
The Cubs are building for the future with Rizzo and rookie right-handed hitters Javier Baez and Jorge Soler. Chicago was 31-28 since July 28.