After compiling a combined 0–1 record with a 3.95 ERA in five starts between both teams,[13] Mize was shut down for the rest of the season due to an innings limit.

[16] After making four starts for Lakeland with an 0.35 ERA, the Tigers promoted Mize to the Erie SeaWolves of the Double–A Eastern League.

[17] In his first start for Erie, he tossed a no-hitter, in which he hit a batter, walked another, and struck out seven on 98 pitches, in a 1–0 SeaWolves victory over the Altoona Curve.

[19] On August 19, 2020, Mize was promoted to the major leagues by the Tigers and made his MLB debut that evening against the Chicago White Sox.

[20][21][22] Mize threw 73 pitches over 4+1⁄3 innings in his first start, allowing three earned runs while striking out seven and walking none in a no-decision.

[23] On September 11 against the Chicago White Sox, Mize took a no-hitter into the sixth inning, before a double by Yolmer Sánchez ruined the no-hit bid.

[24] With the 2020 Detroit Tigers, Mize appeared in seven games, compiling a 0–3 record with 6.99 ERA and 26 strikeouts in 28+1⁄3 innings pitched.

[26] On April 12, Mize earned his first major league win, throwing seven scoreless innings in the Tigers' 6–2 victory over the Houston Astros.

[27] In an August 24 road game against the St. Louis Cardinals, Mize made his major league debut as a batter, and collected an RBI on a bases-loaded walk.

Entering the 2024 season, Mize made the Tigers' Opening Day roster as part of their rotation, beating out Matt Manning for one of the final spots.