Schwarber began the 2015 season with the Double-A Tennessee Smokies of the Southern League. In July 2015, he played in the All-Star Futures Game, where he was named the MVP of the game after hitting a go-ahead two-run triple for Team USA.
The Cubs promoted Schwarber to the major leagues on June 16, 2015, to serve as a designated hitter for six games during interleague play. Schwarber made his major league debut as a position player that night, replacing ejected starting catcher Miguel Montero in the eighth inning against the Cleveland Indians. The following night, as a designated hitter, he got four hits in five at bats with two RBIs and six total bases. The Cubs sent Schwarber to the Triple-A Iowa Cubs of the Pacific Coast League after the six games. On July 16, 2015, Schwarber was recalled from Triple A Iowa, to rejoin the Cubs due to an injury to catcher Montero. On July 21, in a 5–4 extra-inning victory over the Cincinnati Reds, Schwarber hit a game-tying 2-run homer in the ninth inning and a solo go-ahead home run in the top of the 13th to give the Cubs the lead. Schwarber's three multihomer games are the most for a Cub rookie in his first 51 games played since 1914. Over the course of the season he split time between catcher and outfield positions. He finished the 2015 regular season having played 69 games, recording a .246 batting average with 16 home runs, 52 runs scored, and 43 RBIs in just 273 plate appearances. In the National League Wild Card Game, Schwarber drove in three runs and hit a long two-run home run to help the Cubs defeat the Pittsburgh Pirates, 4–0, and advance to the Division Series against the St. Louis Cardinals. In the NLDS, Schwarber helped the Cubs to a 3-1 series victory with 2 home runs, including a mammoth game 4 shot that landed on top of the new Wrigley Field scoreboard in right field. The ball was removed during the 2015-16 off season to prevent theft but was encased in Plexiglas and returned "to where it landed". In his eighth career postseason game, a 5-2 loss to the New York Mets in game 3 of the 2015 National League Championship Series (NLCS), Schwarber set a Cubs record with his fifth career postseason home run and also the record for the most home runs in a single postseason by a player age 22 or younger, passing Miguel Cabrera.