Despite hitting into the wind, the Cardinals crushed five home runs off Cubs starter Travis Wood and St. Louis took the opener of a three-game set, 9-6.
Matt Holliday, Yadier Molina, Lance Berkman, Matt Carpenter and Allen Craig all homered for the Cards, who have won four in a row.
"I still stand by the fact that this is not a home run-hitting team because we don't have a bunch of guys that go up there looking to hit the home run," Cardinals manager Mike Matheny said. "We have some well-rounded hitters that have power and whenever you can mix five home runs into five innings, that's pretty impressive."
Lance Lynn (13-4) improved to 4-0 in his career against the Cubs, although he struggled to get there. Chicago, which scored just two runs in 21 1/3 innings against Lynn coming into Friday's game, tagged the right-hander for six runs on eight hits in five innings.
"It was hit or miss," Lynn said. "Seems like whenever there was runners on they got the hit, and before I was able to make a pitch to get out of it, today I wasn't."
Wood (4-6) had another rough start, lasting only five innings and allowing eight runs on seven hits, including the five blasts. In his last three starts, Wood has allowed 22 earned runs.
"He does have to keep the ball down," Cubs manager Dale Sveum said. "You're going to get away with that a little bit more on some other teams and stuff like that. But this team, there's a reason why those left-handed numbers are what they are with this team. You make a mistake and they don't miss it."
"It's nice that it is, after these past three, because I can look back and be like, 'I know I can still do this,'" Wood said. "The confidence is still there."
Starlin Castro picked up three hits and Anthony Rizzo hit his sixth home run as the Cubs lost their fifth straight game against St. Louis.
The Cardinals homered in each of the first five innings, a club record, with Holliday destroying a solo home run to open the scoring in the first.
Chicago responded with three runs in the bottom half of the first when Castro drove in David DeJesus with a base hit and Rizzo launched a low fastball into the bleachers in right field.
After Berkman singled to start the second, Molina jumped on a first-pitch fastball and drove it beyond the left-field stands onto Waveland Avenue to tie the game.
Following the home run, Carpenter worked a walk and Daniel Descalso lined a triple into the right-field corner to give St. Louis the lead. Lynn lofted a sacrifice fly to center field to score Descalso and make it 5-3.
After Berkman homered in the third to expand St. Louis' lead to three, the Cubs tied the game in the bottom half of the inning.
Castro tripled to start the third and Rizzo punched a base hit through the left side to score him. Alfonso Soriano followed with a double to plate Rizzo, then scored when Geovany Soto lined a single into center field to tie the game.
St. Louis quickly regained the lead in the fourth inning and never looked back. Carpenter led off the inning and slammed a first-pitch fastball over the right-field fence, giving the Cardinals a 7-6 lead.
Craig hit a solo homer in the fifth to give the Cards a two-run lead and Holliday capped the scoring in the seventh when he drove in Jon Jay with a base hit, making it 9-6.
The Cubs were able to bring the tying run to the plate in the eighth inning, but Marc Rzepczynski induced a pair of flyouts to end the threat.
Jason Motte worked around a one-out single to pick up his 23rd save of the year.
Brian Fuentes, who was signed by the Cardinals on July 14, made his St. Louis debut, tossing a perfect sixth inning and fanning two...The Cubs honored recent Hall-of-Fame inductee Ron Santo prior to the game...Rizzo leads National League rookies with six home runs and 15 RBI since June 26...The Cardinals went 1-for-2 with runners in scoring position and stranded four...The Cubs went 3-for-8 with runners in scoring position and left four on base...Wood tied a Cubs record with five home runs allowed.