Wainwright allowed two runs, struck out six and walked one while improving to 4-0 for the first time in his career. The 6-foot-7 right-hander tossed a four-hitter in a 7-2 victory over Cleveland on his 39th birthday in his previous start.
''I don't feel 39,'' he said. ''I felt 39 when I was 34 or 35. When I go out on the mound, I feel good and ready to win.''
Paul DeJong drove in two runs for St. Louis, which had dropped two in a row. Kolten Wong had two hits and scored twice.
Chicago had won four of five. The NL Central leaders had one last chance in the seventh, putting two runners on with two out, but Giovanny Gallegos struck out Anthony Rizzo to finish his third save.
Ian Happ homered twice, but the rest of the Cubs lineup came up empty. Happ started in center field after he missed the series opener with a right eye contusion. He was struck by a foul ball after it bounced off the plate on Thursday in Pittsburgh.
Chicago loaded the bases with none out in the second and failed to score. Wainwright struck out Steven Souza Jr., got Nico Hoerner to line out to second and coaxing Happ into an inning-ending grounder.
''We've got to move the baseball in that situation, make something happen,'' manager David Ross said. ''The strikeout kills you, obviously.''
Cubs right-hander Albert Alzolay (0-1) was pulled after he walked five in 2 2/3 innings in his third appearance this season. He was charged with two runs and two hits.
Happ, batting left-handed, drove Wainwright's second pitch of the game down the line in right for a 1-0 Cubs lead.
It was Happ's major league-best fourth leadoff homer this season.
St. Louis responded with two in the third. DeJong had a run-scoring fielder's choice, and Matt Carpenter followed with a bases-loaded walk, chasing Alzolay.
The Cardinals added two more in the fourth. Tommy Edman had a sacrifice fly, and DeJong made it 4-1 with a two-out RBI single.
Happ hit his 12th homer in the fifth, belting a deep drive to left.
Souza went 0 for 2 with two strikeouts, and then was designated for assignment before the second game of the doubleheader. Souza hit .148 (4 for 27) in 11 games with the Cubs this season.
Right-hander Tyson Miller was recalled from the team's alternate training site in South Bend, Indiana.
The Cubs also claimed infielder Ildemaro Vargas off waivers from Minnesota before the doubleheader opener. Vargas hasn't reported to the club yet.
KIM PLACED ON IL
St. Louis placed Kwang Hyun Kim on the 10-day injured list, a day after the left-hander was taken to a hospital with adominal soreness. Kim was diagnosed with a kidney ailment. He is expected to return to St. Louis on Sunday.
''Thankfully, it wasn't appendicitis, but there's something going on in his kidney,'' manager Mike Shildt said. ''He was in a fair amount of pain yesterday, but that pain has been able to be managed. He's feeling somewhat back to normal. He's not in as much discomfort as he was.''
Kim is 2-0 with a save and a 0.83 ERA in five games this season. He was scheduled to start Sunday night.
Cardinals: LHP Andrew Miller (shoulder fatigue) was activated from the injured list.
Each team planned to go with a bullpen game for the second part of the doubleheader.
Cubs left-hander Jon Lester (2-1, 5.11 ERA) starts the fourth game of the five-game series Sunday night, looking to bounce back from a rough stretch. He is 0-1 with an 8.55 ERA over his last four starts. Right-hander Dakota Hudson (1-2, 2.77 ERA), who originally was slated to start Game 2 on Saturday, will start for St. Louis.
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