Wetherholt will start at second base and bat leadoff in Thursday's opener versus the Rays.
The Cardinals will not ease Wetherholt into his major-league debut, putting him atop their batting order. The team's other potential option in the leadoff spot, Masyn Winn, will hit cleanup. Wetherholt earned a spot on St. Louis' Opening Day roster by collecting a .386 on-base percentage with two home runs and two stolen bases during Grapefruit League action.