On March 18, 2016, the Tigers optioned Fulmer to the Triple-A Toledo Mud Hens. Fulmer was called up and made his major league debut on April 29, against the Minnesota Twins. Fulmer earned the win in his debut, allowing two earned runs over five innings and striking out four in a 9–2 Tigers victory. On May 21, Fulmer had his first home start at Comerica Park in Detroit, where he gave up just one earned run and recorded 11 strikeouts over seven innings, defeating the Tampa Bay Rays. Fulmer became the first Detroit Tigers rookie pitcher to strike out 11 opposing batters in one game since Pat Underwood in 1979. On June 1, Fulmer no-hit the Los Angeles Angels of Anaheim for 6 ⁄3 innings before surrendering a two-out single in the 7th to C. J. Cron. He wound up allowing two hits and no runs over 7 ⁄3 innings. On June 6, Fulmer pitched six scoreless innings, while allowing only two hits against the Toronto Blue Jays. Fulmer became the first pitcher in Tigers history to pitch three consecutive scoreless outings of six innings or more while allowing three or fewer hits.
Fulmer married girlfriend Kelsey Miles in January 2016. He works as a plumber's assistant during the offseason.