The slugger had been on the disabled list since June 26 due to left shoulder inflammation.
Infielder David Bote was optioned to Triple-A Iowa to make room for Bryant.
When the shoulder became an issue, Bryant said extra time in the batting cage caused the soreness, but when he went on the DL he said he originally hurt it about a month before on a slide.
Bryant has been solid this season, but the former MVP struggled in June. He is batting .280 with nine homers and 36 RBIs.
The Cubs had just lost their fifth in a row when Bryant went on the DL, but they have turned it around since then with a 10-3 record. The Cubs were trying to take two of three games by winning the rubber game Wednesday afternoon in San Francisco.