On August 1, 2016, the Pirates traded Liriano along with Reese McGuire and Harold Ramírez to the Toronto Blue Jays for Drew Hutchison. While it was initially believed that Liriano would replace Aaron Sanchez in the rotation due to the organization's desire to limit Sanchez's workload, general manager Ross Atkins announced on August 4 that the Blue Jays would use a six-man rotation going forward. Liriano made his debut with the Blue Jays on August 5, pitching six innings against the Kansas City Royals and yielding two earned runs in a 4–3 win. He made eight starts and two relief appearances with the Blue Jays in the regular season, and posted a 2–2 record, 2.92 ERA, and 52 strikeouts in 49 innings. In 2016 between the two teams he had the highest rate of bases on balls per 9 innings pitched in the majors (4.69).