Ludwick, who now has 23 RBIs in just 97 at-bats, snapped a streak of 13 consecutive scoreless innings by Brewers relievers.
Cardinals starter Joel Pineiro pitched superbly and walked off the field with a 3-0 lead, but Prince Fielder's solo home run in the eighth off Ron Villone tied the score at 3 and ignited replays of the night before. In that game, the Brewers rallied back from a 3-0 deficit before scoring twice in the ninth against Isringhausen to win, 4-3.
"We've done that several times now where as a team, the day before you get your heart broken and the next day, you come back absolutely fresh," Cardinals manager Tony La Russa said. "The character is outstanding. That was really a tough-it-out win."
Fielder's shot leading off the eighth was the first hit by a left-hander in 17 at-bats against Villone. St. Louis escaped further damage in the frame when batter Jason Kendall missed the sign for a squeeze play, allowing the Cards to get an out on the bases and ultimately escape a bases-loaded, one-out situation.
St. Louis then followed suit against Gagne (1-2) by loading the bases with one out before Rick Ankiel fouled out to Fielder. That set the table for Ludwick.
"The pitch before the hit was a curveball, and so I figured I was going to see splitter or fastball on the next pitch," Ludwick said. "It was down and away, and I stuck my bat head out there and found the hole."
Russ Springer (1-0) came away with the victory, and Ryan Franklin recorded his second save after inheriting the closing reins -- at least for one day -- from Isringhausen.
Pineiro allowed just two hits through his first six innings before running into trouble in the seventh. He left having tossed 6 1/3 innings, with two runs allowed on four hits, three walks and three strikeouts.
"The sinker was so amazing today," Pineiro said. "It's been a long time since I had a good sinker like that. You just have to take advantage of it. I told the infield, 'You're going to get a lot of ground balls.' We had great infield defense. It was just a great team win."
Kyle McClellan endured a rocky outing in relief of Pineiro in the seventh after entering with the bases loaded and one out. The right-hander walked Kendall on four pitches to force in a run, then fumbled a comebacker by Rickie Weeks that could have produced an inning-ending double play. Catcher Yadier Molina still picked up the ball in time for the force at home plate.
McClellan got ahead of Mike Cameron, 0-2, before issuing another walk to make the score 3-2. Ryan Braun then flied out.
Chris Duncan, who entered the game hitting 7-for-12 in his career against Brewers starter Ben Sheets, launched a two-run homer that curled just inside the right-field foul pole in the fourth, giving the Cardinals their 3-0 lead.
"He's doing so much work and he's so close, he needed something to keep him going, and he got that today," La Russa said of Duncan. "That was a big home run against a guy who's pitching as well as anybody in Major League Baseball."
Yadier Molina singled and scored on a groundout in the third to initiate the scoring. Troy Glaus, who sat out the game with a bruised triceps, pinch-hit in the contest and figures to be ready for Sunday's game.