The right-hander held the National League leaders to three runs and six hits in 6 2/3 innings, with five strikeouts against one walk. It marked his third quality start in a row.
Wellemeyer (9-4) is beginning to look like the upstart who had a 7-1 record in June before right elbow soreness threw a wrench into an impressive season.
"I think he's healthy," Cardinals manager Tony La Russa said. "I think he's also been out there enough now that he's regained his delivery and sharpness. Like [Braden] Looper yesterday, that was an outstanding performance."
La Russa skipped Wellemeyer in one rotation turn in June, then the pitcher took about a month to regain his consistency. He may be better now than before the injury.
"I've added some stuff," Wellemeyer said. "My changeup, it's the best I've felt with that pitch in the last three starts all year."
Mark DeRosa and power-hitting pitcher Carlos Zambrano homered for the Cubs on Saturday, but Wellemeyer kept the scoring minimized while his offense poured it on.
Alfonso Soriano led off the game with a single, and Chicago put runners on the corners with one out in the third. He escaped both times.
"Two of the biggest things that happened was that zero in that first inning [and the double play]," La Russa said. "When that leadoff guy gets on, they score a lot. Retire the third and fourth hitter and get that zero, and that double play was big."
He baffled every Cubs hitter, with the possible exception of the Silver Slugger Zambrano, who has remained tight with Wellemeyer since their Cubs days.
Zambrano took a 3-1 fastball to the opposite-field bleachers in the third to trim St. Louis' lead to 3-2. Wellemeyer may have been taking it easy on his buddy.
"I didn't want to get too nasty on him because he gave me all fastballs, so I gave him all fastballs," Wellemeyer said.
That didn't surprise Zambrano, a .364 hitter.
"I knew he was coming with a fastball," Zambrano said. "He pitched good today -- Shoulders, he did a good job."
Wellemeyer, nicknamed "Shoulders" by Zambrano for his built upper body, got the best of the Cubs' ace in the decision. To him, that was almost as sweet as winning in his former home ballpark.
"Especially against Zambrano, that was awesome," Wellemeyer said. "I guess he wasn't really feeling up today."