The All-Star right-hander now visits the North Side, where he's never lost.
Wainwright tries to extend his 25-inning scoreless streak as the Cardinals open a three-game set at Wrigley Field on Friday.
Wainwright (5-1, 1.20 ERA) has been sensational in the early going, striking out 42 and walking 11 over 45 innings while holding opponents to a .157 average. He already has four scoreless outings under his belt, and his ERA ranks second in the majors.
"I'm really having more fun pitching right now than I ever have," he said. "I'm right where I want to be and so I'm going to work extra hard to stay there and not get complacent."
Wainwright has only allowed six runs thus far, and he hasn't surrendered any since giving up four over seven innings in a 10-4 win over the Cubs on April 12. He joined Darryl Kile, Bob Tewksbury and John Denny as the only Cardinals pitchers to win five games through April after throwing eight innings of three-hit ball in Sunday's 7-0 victory over Pittsburgh.
Instead of going with a fifth starter, St. Louis moved Wainwright up a day following Thursday's day off.
"He was excited to get back out there on regular rest and kind of stay in the groove that he's been in," manager Mike Matheny said. "I think we can all agree that he has been throwing the ball exceptionally well, and sometimes staying in that routine can be a benefit."
Wainwright has a 2.33 ERA during his three-start winning streak versus Chicago, striking out 24 in 19 1-3 innings. He is 6-0 in 16 games - 11 starts - at Wrigley, yielding one or two runs in six of his last eight outings there.
The Cardinals (15-14) are opening a nine-game road swing after closing a 3-3 homestand with Wednesday's 9-3 win over Milwaukee. Allen Craig went 4 for 5 with a solo homer and three RBIs, and Matt Adams belted a three-run homer as St. Louis avoided a sweep.
"It was good to see all aspects of our game click today," Adams said. "When we click with everything, we're a good team."
The Cubs (9-17) return home after splitting a rain-shortened two-game set at Cincinnati. Anthony Rizzo hit a two-run homer and drew a career-high four walks in Wednesday's 9-4 victory.
Starlin Castro also came up big with three hits for Chicago, which had scored just 13 runs while hitting .191 in its previous five games.
"We've been having a tough time trying to tack on runs and score runs," manager Rick Renteria said. "Today was an example of what we can do."
The Cubs now turn to Travis Wood (1-3, 3.52), who gave up all five runs in Saturday's 5-3 loss at Milwaukee. The left-hander allowed seven hits and walked three in 5 2-3 innings.
"He didn't stay down in the zone as well as he normally does," Renteria said. "He has the ability and had been working down in the zone quite well since the beginning of the season."
Wood could benefit from returning home, where he's gone 1-0 with a 1.38 ERA while striking out 18 in his last two outings spanning 13 innings.
However, Wood is 0-3 with a 6.16 ERA during a four-start stretch against the Cardinals. He's been hit hard by Yadier Molina, who is 11 for 24 with three homers and three doubles in their matchups since 2011.
The Cardinals have won seven of 11 in Chicago.
"I just love the atmosphere," Matheny said. "I love the hatred that the Cubs fans have for us. That makes for some of the most interesting fan interaction you can possibly have."