Wainwright's Monday start is his first since May 13 in San Diego, after which he went to the disabled list with elbow discomfort. He started the season 1-3 with a 4.00 earned-run average.
In his career against Pittsburgh, the 37-year-old Wainwright is 13-7, but has an ERA of 4.28. He threw 17 scoreless innings over six rehab appearances.
"It's... we're pretty excited,'' Cards manager Mike Shildt said in the dugout prior to Monday's game. "Last night, getting off the plane, I turned to him and said, 'You get to pitch tomorrow' and there was this look in his eyes, just pure joy and excitement.