On July 22, 2021, while JOE RYAN was in Tokyo competing in the 2020 Summer Olympics, he was traded alongside Drew Strotman to the Minnesota Twins in exchange for Nelson Cruz and Calvin Faucher. After making 2 starts for the Triple-A St. Paul Saints, posting an ERA of 2.00 with 17 strikeouts, the Twins selected Ryan's contract when the rosters expanded. Ryan made his MLB debut on September 1, 2021, starting against the Chicago Cubs. He pitched 5 innings, gave up 3 runs, and struck out 5. On April 1, 2022, manager Rocco Baldelli announced that Ryan would be the 2022 Opening Day starting pitcher and start his first career Opening Day against the Seattle Mariners. Despite missing a month due to injury, Ryan had a career year as he led the team in wins (13), strikeouts (151) and innings pitched (147). On the 2023 season, Ryan took a step back from his performance the year before. Despite striking out 197 in 161+2⁄3 innings, he allowed 32 home runs and his ERA grew a run higher (4.51).