Manoah made his debut against the New York Yankees and secured a win with a final score of 20, also notching his first MLB strikeout against Rougned Odor. Manoah finished the game with seven strikeouts, two walks, no runs, and two hits allowed over six innings. However, he faced a five-game suspension on June 22 due to an incident from a game on June 19 where he intentionally hit Maikel Franco with a pitch. On July 2, Manoah set a Blue Jays franchise record by striking out seven consecutive batters against the Tampa Bay Rays. His rookie season concluded with impressive stats, starting twenty games with a record of 92, an ERA of 3.22, and 127 strikeouts over 111 innings.
In 2022, Manoah was selected for the MLB All-Star Game and pitched a scoreless inning with three strikeouts. He had a standout season with a 167 record, a 2.24 ERA, and 180 strikeouts in 196 innings. Despite his successes, the year ended disappointingly as the Blue Jays were swept in the Wild Card Series by the Seattle Mariners, and Manoah finished third in Cy Young Award voting.
The following season began with high expectations for Manoah, named as Toronto's opening day starter. However, he struggled early on, posting a 6.36 ERA in his first 13 starts. His performance hit a low point in a game against the Houston Astros on June 5, 2023, where he allowed six runs in the first inning before being pulled from the game. This led to his demotion to the Florida Complex League the next day.
After a month in the minors, Manoah returned to the major league club on July 7 and earned a win in his first start against the Detroit Tigers. However, he faced challenges in subsequent starts and was eventually sent down to AAA Buffalo after a loss on August 10. Manoah reacted poorly to the demotion, refusing to report to the Bisons and informing the Blue Jays that he would not pitch again for the rest of the 2023 season.
