After his senior season, Mantiply was drafted by the Detroit Tigers in the 27th round of the 2013 MLB Draft.[8] He made his professional debut that season with the Connecticut Tigers. After starting his career as a starting pitcher, Mantiply became a relief pitcher in 2014. He started the season with the West Michigan Whitecaps and was later promoted to the Double-A Erie SeaWolves.[9][10][11] Mantiply was called up and made his major league debut on September 3, 2016.
New York Yankees
On November 8, 2016, Mantiply was claimed off waivers by the New York Yankees.[12] He was released on November 28,[13] and signed a new minor league contract with the team on November 30.[14] Mantiply spent the 2017 season with the Triple–A Scranton/Wilkes-Barre RailRiders, making 35 appearances and registering a 6–5 record and 2.83 ERA with 62 strikeouts across 70 innings pitched. He elected free agency following the season on November 6, 2017.[15]
Cincinnati Reds
On November 13, 2017, Mantiply signed a minor league contract with the Cincinnati Reds.[16] On March 9, 2018, Mantiply underwent Tommy John surgery, and was ruled out for entirety of the season.[17] On October 11, 2018, Mantiply re–signed with the team on a minor league deal for the 2019 season.
New York Yankees (second stint)
On August 9, 2019, Mantiply was traded to the New York Yankees in exchange for cash considerations. On August 11, the Yankees selected Mantiply's contract.[18] He made his 2019 debut on August 12, against the Baltimore Orioles. He earned his first major league win after relieving Chad Green for three innings.[19] On August 13, Mantiply was designated for assignment.[20] He elected free agency following the season on November 4.[21]
Arizona Diamondbacks
On January 20, 2020, Mantiply signed a minor league deal with the Arizona Diamondbacks. On September 1, the Diamondbacks selected Mantiply's contract to the active roster.[22] With the 2020 Arizona Diamondbacks, Mantiply appeared in 4 games, compiling a 0–0 record with 15.43 ERA and 2 strikeouts in 2.1 innings pitched.[23] On September 28, Mantiply was designated for assignment by the Diamondbacks.[24] He re–signed with Arizona on a minor league deal on November 2. On May 15, 2021, Mantiply was selected to the active roster.[25]
In 2022, Mantiply was named to the National League All-star team as a reliever. It was his first All-star selection.[26]