Baker started on Opening Day for the Twins to kick off the 2010 season against the Angels but allowed four runs in innings, taking the loss in a 6–3 defeat. He won his next start, allowing one run in seven innings in a 2–1 victory over the Chicago White Sox on April 10. Through May 8, he went 4–2. On June 16, Baker struck out a career-best 12 batters through seven innings in a 2–1 victory over the Colorado Rockies. He picked up his 50th career win on July 2, allowing one run in seven innings in a 2–1 victory over the Tampa Bay Rays. On August 10, he allowed five runs (four earned) in six innings but earned his 10th win of the season in a 12–6 victory over the White Sox. He left a start with elbow pain on September 2 and did not pitch again until September 21. Baker finished the season on a 9–1 stretch and helped the Twins repeat as winners of the AL Central. In 29 starts, he had a 12–9 record, a 4.49 ERA, and 148 strikeouts in innings. During the season, he moved from 22nd to 12th all-time on the Twins' strikeout list. Baker was left out of the Twins' postseason rotation, though he was a member of their bullpen. He made his playoff debut in Game 3 of the ALDS, allowing one run in innings as the Twins were again swept by the Yankees.