Cardinals slugger Matt Holliday hadn't homered in 10 weeks, but he knew immediately he really nailed one.

Holliday hit his sixth career grand slam off White Sox starter Carlos Rodon's first pitch to him in the fourth inning, powering Michael Wacha and St. Louis past Chicago 8-5 on Tuesday night.

Holliday connected for the first time since May 12, recording just his fourth homer this season. He returned last Friday after missing 31 games because of a strained right quadriceps.

"I've hit a few of them," Holliday said. "I knew I got it pretty good.

"I'm just trying to be aggressive early, trying to get something to hit hard, preferably in the air."

Although Holliday is under orders not to push his injured thigh too hard, he didn't have to after his drive sailed deep into the left-center field bleachers and staked the Cardinals to a 7-0 lead. He added a single and scored a second run in going 2 for 4.

"It was great to see him hit a ball like he can," St. Louis manager Mike Matheny said. "We just like having him back on our club. He's just a big piece."

Mark Reynolds added a solo shot in the fifth.

Wacha (11-3) gave up five runs in five innings. Trevor Rosenthal pitched the ninth for his 28th save in 30 chances.

Wacha retired the first nine he faced before giving up all five Chicago runs in the fourth and fifth. Matheny pulled him after the fifth and 100 pitches.

"I felt really good throughout he first three, then just left some balls up in the zone," Wacha said. "I lost control of fastball command and they didn't miss the mistakes the last couple of innings I was out there."

Stephen Piscotty, St. Louis' top hitting prospect, made his major league debut playing left field. He had an infield single in four at-bats and struck out twice.

Yadier Molina drove in two runs and Matt Carpenter added an RBI for the Cardinals, who were swept by the White Sox in St. Louis three weeks ago.

Rodon (3-3) was tagged for seven hits in four innings as Chicago lost its third in a row.

"Even the last time out, (Rodon) got himself in some trouble and got out of it," White Sox manager Robin Ventura said. "This one didn't work out that way. Holliday had the big homer that really knocked him out of this one."

White Sox rookie Tyler Saladino homered for the second straight game. He and Geovany Soto homered off Wacha in the fifth.

Four Cardinals relievers combined for four scoreless innings, handing the White Sox their fourth loss in five games since the All-Star break.

Carpenter ended an 0-for-17 slump with an RBI single in the second.