Devers resumed his role as Boston's regular third baseman for 2019. On June 3, he was named the AL Player of the Month for May, having batted .351 with eight home runs during the month. On August 13, Devers became the latest MLB player to record six hits in a game; he was 5-for-5 in the first nine innings of an away game against the Cleveland Indians, and had his sixth hit in the 10th inning. In addition, Devers' four doubles in his 6-for-6 night make him the only player since 1900 to record six-plus hits with at least four doubles. On August 18, Devers became the first MLB player to record 100 RBIs during the 2019 season. He was named AL Player of the Week for the week of August 12–18. On September 21, Devers hit his 31st home run of the season, setting a new Red Sox franchise record for home runs by a third baseman in a season, passing Butch Hobson who had hit 30 in 1977. On September 29, the final day of the regular season, Devers reached the 200-hit plateau.

He finished the season with 201 hits and a .308 average, along with 54 doubles (leading the AL), 32 home runs, and 115 RBIs, and led the major leagues with 90 extra base hits and 359 total bases. He finished 12th in 2019 AL MVP voting.

This Rawlings official MLB baseball was signed in blue by Devers and includes a Fanatics hologram.