Rodriguez batted fifth and started at third base against the Blue Jays, his first appearance since Sept. 9 at Seattle.
Rodriguez, who is batting .284 with 15 homers and 56 RBI, will hit with a half-inch strip of tape on the handle of his bat. The tape, which Rodriguez used during batting practice Friday, acts as a pad between his hands, relieving pain and pressure on his thumb.
A 14-time All-Star and three-time AL MVP, Rodriguez has been limited to 90 games. He had arthroscopic surgery on his right knee in July, which sidelined him for 38 games.
The 36-year-old Rodriguez is two home runs shy of Ken Griffey Jr. for fifth place on the career list.