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Pannone opened the 2019 season with the Blue Jays as a member of the bullpen. On April 14, Pannone pitched an immaculate inning against the Tampa Bay Rays, striking out Avisail Garcia, Brandon Lowe, and Daniel Robertson on 9 consecutive strikes. It is the third immaculate inning in Blue Jays team history; Steve Delabar and Roger Clemens are the other two who have managed the feat.

On March 16, 2018, Pannone was suspended for 80 games after testing positive for dehydrochlormethyltestosterone, a banned performance-enhancing substance. After returning from suspension, he was assigned to the Triple-A Buffalo Bisons. On August 9, Pannone was called up by the Blue Jays. He made his first MLB start on August 22, and took a no-hitter into the seventh inning against the Baltimore Orioles. Pannone recorded the win, allowing just one hit and two walks with three strikeouts in seven innings. Pannone totaled 12 appearances for the Blue Jays, 6 of them starts, recording a record of 4-1 in 43 innings.

Pannone was assigned to Advanced-A Lynchburg to open the 2017 season. In early May he was promoted to the Double-A Akron RubberDucks, and was named an Eastern League All-Star at mid-season.

On July 31, 2017, Pannone was traded, along with Samad Taylor, to the Toronto Blue Jays for Joe Smith. He was assigned to the Double-A New Hampshire Fisher Cats, and remained there for the rest of the 2017 season. On the year, Pannone posted a 9–3 record, 2.36 ERA, and 149 strikeouts in 144​⁄3 innings. On November 20, 2017, Pannone was added to Toronto's 40-man roster.

Pannone was selected by the Cleveland Indians in the ninth round of the 2013 Major League Baseball draft. He made his professional debut with the Rookie-level Arizona League Indians. He made 14 relief appearances in 2013 and pitched to a 1–0 record, 9.00 ERA, and 20 strikeouts in 16 innings. He remained in the Arizona League for the 2014 season, going 5–0 with a 3.20 ERA and 62 strikeouts in 45 innings, and was named a post-season All-Star by the league. Pannone made his full-season debut in 2015, pitching the entire season with the Class-A Lake County Captains. In 116​⁄3 total innings over 27 appearances, he posted a 7–6 record, 4.02 ERA, and 120 strikeouts. Pannone began the 2016 season with Lake County, where he was named a mid-season All-Star, before being promoted to the Advanced-A Lynchburg Hillcats in July. In total, he made 25 appearances in the 2016 season and went 8–5 with a 2.57 ERA and 122 strikeouts in 133 innings.

Pannone attended Bishop Hendricken High School in Warwick, Rhode Island, where he was an outfielder as well as a pitcher. He was drafted by the Chicago Cubs in the 33rd round of the 2012 Major League Baseball draft, but did not sign and attended the College of Southern Nevada. Pannone stopped playing outfield in college, focusing solely on pitching. In his lone season of college baseball, he posted a 6–2 win–loss record, 1.84 earned run average (ERA), and 78 strikeouts in 53​⁄3 innings pitched.

Thomas Edward Pannone (/p ɑː ˈ n oʊ n / pah-NOHN ; born April 28, 1994) is an American professional baseball pitcher for the Toronto Blue Jays of Major League Baseball (MLB).