Wieters began the 2015 season on the 15-day disabled list in an effort to continue recovering from last year's Tommy John surgery. Wieters returned to the Orioles on June 5 and became an immediate impact in their lineup. On July 27, Wieters hit his fourth career walk-off home run, helping the Orioles's beat the Atlanta Braves by a score of 2–1. Wieters would end up slashing .267/.319/.422 in 75 games for the Orioles in 2015. He collected 69 hits, eight home runs, and also drove in 25 runs.