Wainwright, a first-round draft choice (29th overall) of the Atlanta Braves in 2000, is 7-0 in seven home starts this season, posting a stingy 1.67 earned run average across 54 innings in familiar surroundings.
His most-recent win in St. Louis came June 19 against Oakland as he scattered five hits and gave up a single unearned run in a 4-3 defeat of the Athletics.
He's just 3-5 in nine road starts this season and lasted just four innings in a 5-0 loss at Toronto in his last outing on June 24.
The 29-year-old Georgia native has faced the Diamondbacks eight times in 165 career big-league appearances, going 3-3 with a 2.94 ERA while walking 15 batters and striking out 23.
St. Louis rallied to win Monday's series opener when Aaron Heilman and Adam LaRoche committed costly errors in the ninth inning, the latter of which scored two runs to give the Cardinals a 6-5 win.
Arizona's Dan Haren pitched into the ninth inning and belted the go-ahead homer leading off the seventh, but the Diamondbacks couldn't hold on and lost for the 17th time in their last 20 road games.
Yadier Molina and Brendan Ryan singled to start the bottom of the ninth. Heilman (2-2) then entered from the bullpen to face a pinch-hitting Wainwright, who put down a sacrifice bunt to the left side of the infield. Heilman bare-handed the ball, but his throw to third bounced and was wide of the base, allowing pinch-runner Jaime Garcia to score for a 5-4 margin.
The Diamondbacks played their infield in and it initially paid off when Randy Winn grounded out to shortstop, keeping the runners at second and third. Skip Schumaker then grounded a ball sharply to first base. Instead of stepping on the base and giving up the tying run, LaRoche came home with the throw, but it bounced by catcher Miguel Montero, giving the Cardinals the win as Ryan and Wainwright scored easily.
Haren was on target for the win after allowing 10 hits and five runs -- three earned -- but the 2001 first-round pick by the Cardinals was derailed thanks to the miscues.
Cardinals starter Chris Carpenter, who came into the game 5-0 over his last eight appearances and 4-0 in 10 lifetime games (nine starts) against Arizona, was charged with six hits and three runs over seven innings.
LaRoche and Mark Reynolds each hit two-run homers for Arizona, while Felipe Lopez had two hits and an RBI for the Cardinals.
The Diamondbacks go tonight with former NL Cy Young Award winner Dontrelle Willis, who's won once in four starts since coming over from the Detroit Tigers earlier this season.
A 22-game winner with Florida in 2005, Willis skidded to 12 and 10 wins in the subsequent two seasons before heading to the Tigers, where he won just twice in 24 appearances through May 28 of this year.
He downed Colorado, 4-3, in his debut with Arizona on June 5 and has gotten no-decisions in three starts since while allowing nine hits and nine runs in 11 1/3 innings.
Willis is 1-3 in five career starts against St. Louis with a 5.53 ERA.
Arizona and St. Louis split six meetings prior to this series.