Blanton won for the first time since joining Philadelphia in a mid-July trade with the Athletics, riding home runs from Ryan Howard and Greg Dobbs to a 2-1 victory on Saturday night.
His biggest strikeout froze Pujols with two on to end the third.
"Sometimes as a starter, those at-bats can kind of be the ones that make or break the game," Blanton said. "I wanted to make tough pitches and hopefully make something good happen."
Dobbs, who leads the majors with 20 pinch hits, hit his fourth homer of the season on the first pitch of the third from Braden Looper (10-9). Howard hit his 31st for his National League-leading 96th RBI with two outs in the fourth.
The NL East-leading Phillies have homered in 11 straight games, totaling 19, and have won six of seven.
"They've got a really good lineup and if you make mistakes they make you pay," Looper said. "Unfortunately I made one too many, and it's kind of a tough one to swallow."
Howard, who is from the St. Louis suburb of Wildwood, also walked three times and is 12-for-27 (.444) against the Cardinals this season, with six homers, 15 RBI and eight walks. For his career, he's batting .363 against St. Louis with 12 homers and 32 RBI, and he's 4-for-5 against Looper with three homers and five RBI.
"I don't know if we want to play the Cardinals every day, because they're pretty good, but Howard seems to play pretty good against them," manager Charlie Manuel said. "I think he feels comfortable here. He's around his people and he's relaxed."
Howard said his manager's comments were right on the money.
"You grew up playing here in front of your family and friends," Howard said. "To be able to do it at the major league level, it's just like playing back when you were 15."
Knowing his history against Howard, Looper said he tried to mix things up. To no avail.
"Every mistake I throw to him, he seems to hit out of the ballpark," Looper said. "I'm kind of mad at myself. I went into that game not wanting Ryan Howard to beat me and he ended up kind of beating me."
Ryan Ludwick homered for the third time in two games, his 26th overall, for the Cardinals. The drive landed in Big Mac Land, the third deck in left, and was estimated at 427 feet.
"I've been pretty much streaky. I think most power guys are like that," Ludwick said. "You always hear that term, that they come in bunches. But I really only had one good at-bat."
Blanton (1-0) allowed four hits in seven innings and all five of his strikeouts came on called third strikes. He's 6-12 overall and had been saddled with a 6.65 ERA in his previous 12 outings while going 3-6.
"He kept us off balance, moved the ball around the strike zone and just off the strike zone," Cardinals manager Tony La Russa said. "He did a good job of mixing things up."
Chad Durbin got Joe Mather on a double-play ball to end the eighth and Brad Lidge finished for his 27th save in 27 chances and extended his franchise record to 30 in a row dating to Sept. 25, 2007, at Cincinnati.
The Phillies are 49-0 when leading after eight innings and Lidge took care of the heart of the St. Louis order, working around a two-out walk to Troy Glaus and a wild pitch on his first delivery to pinch hitter Rick Ankiel before finishing him off with a strikeout.
Looper is 2-6 with a 5.53 ERA against the Phillies, two of the losses coming this season. He's 1-2 in his last three starts overall despite a 2.37 ERA in that span. ... Ludwick is 12-for-23 (.522) with three homers in his last six games, including two homers in the opener of a three-game series on Friday. ... The Cardinals had a full count against Blanton six times in the first 12 at-bats, and once in the final 14. ... Ankiel missed his seventh straight start with an abdominal strain, and the at-bat was his first since he walked on Tuesday at Atlanta as a pinch hitter.