The Blue Jays selected Mayza in the 12th round of the 2013 Major League Baseball draft, and he made his MLB debut in 2017.

Mayza played baseball, basketball, and soccer for Upper Perkiomen High School in Red Hill, Pennsylvania.

[4][5] The Toronto Blue Jays selected Mayza in the 12th round of the 2013 Major League Baseball draft.

He received a $100,000 signing bonus and was assigned to the Rookie-level Gulf Coast League Blue Jays to begin his professional career.

[10] Mayza was credited with his first major league win on September 12, when he pitched the bottom half of the 9th inning before the Blue Jays walked off the Baltimore Orioles 3–2.

[12] On September 13, 2019, in the 10th inning in a game against the New York Yankees, Mayza threw a pitch behind Didi Gregorius and immediately crumpled to the ground in pain.

On September 28, 2022, Mayza gave up Aaron Judge’s 61st home run, tying an American League record.

He made 63 total appearances for the Blue Jays in 2022, compiling an 8–1 record and 3.14 ERA with 44 strikeouts across 48+2⁄3 innings pitched.

[16] On January 13, 2023, Mayza signed a one-year, $2.1 million contract with the Blue Jays, avoiding salary arbitration.

Mayza began the 2024 campaign out of Toronto's bullpen, and struggled to an 8.03 ERA with 16 strikeouts across 24+2⁄3 innings pitched.