Wainwright allowed a season-high seven runs on eight hits in a season-low 4 1/3 innings, and an eighth-inning rally by the Cardinals' offense was too little, too late as the Giants hung on for a 9-4 win, sending the Cardinals to their third straight loss at Busch Stadium.
"Tonight was just terrible, just not a good night," Wainwright said. "It's unfortunate to go up against a great starter like Madison [Bumgarner] that I did that and gave our team little to no chance to win that game."
Wainwright's undoing came on clutch, two-out hitting from the Giants.
He surrendered a leadoff double in the first inning to center fielder Angel Pagan, but retired the next two hitters. First baseman Michael Morse blooped a single in front of center fielder Peter Bourjos to end Wainwright's scoreless-innings streak at 20.
That was the least of his problems, which mounted an inning later when the two-out hitting continued.
After retiring the first two batters of the second, Wainwright issued a 10-pitch walk to No. 8 hitter Brandon Hicks. Two singles, one by Bumgarner, eventually scored the second run of the game before right fielder Hunter Pence stepped to the plate.
Pence drove a 75 mph curveball 447 feet into the third deck in left field to put the Cardinals in a 5-0 hole from which they would never recover.
"That's the game right there. That inning is the game," Wainwright said. "If I keep it at two, or especially if I keep it at one, we probably win the game."
Wainwright tossed scoreless third and fourth innings, but ran into trouble again in the fifth. With one out, he allowed a single and double to put runners on second and third before he was pulled after throwing 92 pitches.
Reliever Seth Maness retired the first hitter he faced on a grounder to second, but another two-out hit from the Giants drove in two more runs credited to Wainwright's line, his worst since he allowed nine runs last Aug. 28 against Cincinnati.
"He's been the best pitcher in baseball for the last two months," Cardinals manager Mike Matheny said. "Today was just one of those ones you've got to forget about and get right back after it."
"I don't care how good you think you are, the way he's throwing, you don't expect to score runs like that," Giants manager Bruce Bochy added. "But these athletes, they're not going to be on every time. That's why you play."
The Cardinals offense mustered only three hits off Bumgarner, who struck out 10 in seven innings. They advanced a runner as far as third base in the fourth, but a double play ended the inning.
The Giants continued their offensive prowess after Wainwright's departure. Maness allowed a single and double to start the seventh and walked Morse to load the bases. Catcher Hector Sanchez drove a first-pitch changeup to right field to cap San Francisco's scoring with two more runs.
St. Louis loaded the bases in the eighth with two outs off Giants reliever David Huff. Kolten Wong was hit by a pitch, and Daniel Descalso and Randal Grichuk, who got the start after being recalled from Triple-A earlier Friday, both walked.
Jon Jay cleared the bases to put the Cardinals on the board with a line drive to right-center. Allen Craig scored him with a double off the right-field wall after Huff was lifted for Juan Gutierrez.
"When we continue to take those at-bats regardless what the situation is, good things are going to happen," Matheny said. "We still believe that; we just had a long way to come back from."
The loss sent the Cardinals to 1-4 on their current homestand and Wainwright to his worst loss of an otherwise prominent season.
It won't change his perspective, however.
"To overreact to one start would be a mistake," said Wainwright, whose ERA jumped to 2.32. "I'll continue to do my work between starts that I always do to make sure that when I go out there I'll be very prepared next time out. I'll be very focused and I'll be ready to turn the switch on this."
As for answers to what went wrong Friday, Wainwright had no intentions of thinking about it. Sometimes, he said, there just isn't an answer.
"There's things that can't be explained sometimes," Wainwright said. "Just a funny game."