SAN DIEGO (AP) -- With the St. Louis Cardinals leading the San Diego Padres 2-1 in the sixth inning, manager Mike Matheny had seen enough of Shelby Miller.
The rookie right-hander had just walked his second batter of the inning, with two outs, on his 107th pitch. The Padres scored twice to take the lead, sticking Miller with the loss in a 4-2 defeat.
"He hit some real good spots," Matheny said. "But it was one of those games where they fouled off a lot of pitches to get his pitch count up. It was too high to really get himself out of trouble late in the game."
Jason Marquis combined with four relievers on a four-hitter to win his fifth straight start and Will Venable homered to lead the San Padres.
Marquis (6-2) has won five consecutive starts for the first time since 2007 with the Chicago Cubs. He allowed two runs, one earned, on three hits in six innings while striking out three and walking four.
Chris Denorfia went 3 for 3 with an RBI for the Padres, who have won three straight and five of seven. Huston Street pitched the ninth for his 11th save in 12 chances.
Venable homered into the Jack Daniel's Old No. 7 Deck atop the right-field fence leading off the seventh, his seventh. It came on the second pitch from Mitchell Boggs, who just returned from a demotion to Triple-A Memphis.
Miller (5-3) allowed three runs and five hits in 5 2-3 innings, struck out five and walked three.
"It was more just missing my spots and them not swinging," Miller said. "When you face a good-hitting offense, it's not going to be easy to throw it and have them swing at it every single time. It's something I have to realize just to get the ball around the zone."
The Padres scored two runs in the sixth on three walks, one hit and a hit batter.
After Miller was pulled, Denorfia greeted Fernando Salas with an RBI single. John Baker walked to load the bases and Salas hit pinch-hitter Jesus Guzman with a pitch to bring in another run.
"It seems like 20 pitches every single inning, every single outing, back-to-back starts," Miller said. "Throwing so many pitches in back-to-back games is not good. It accumulates with a little bit of everything. My curveball wasn't really good tonight. Neither was my changeup. My fastball wasn't really there. Multiple things were off."
Miller entered with a 1.40 ERA, tied with Clayton Kershaw of the Los Angeles Dodgers for the lowest in the majors. It went up to 1.74. Two starts earlier, Miller allowed a single to start the game and then retired the next 27 batters in a 3-0 home win against Colorado.
Miller's scoreless streak of 14 2-3 innings ended in the first when Everth Cabrera hit a leadoff single and scored on Chase Headley's one-out single.
The Cardinals tied it in the second when Headley, San Diego's Gold Glove third baseman, booted Miller's bases-loaded grounder for an error, allowing Yadier Molina to score. The Cardinals added a run in the third when Carlos Beltran hit a leadoff double, advanced on Matt Holliday's single and scored on Allen Craig's double-play grounder.
San Diego had a prime opportunity to score in its half when Cabrera hit a leadoff triple to right-center. But he was stranded when Miller struck out Will Venable and Headley before Carlos Quentin popped up.
NOTES: Cardinals 3B David Freese was a late scratch due to getting three stitches in the base of his right thumb after getting spiked by Milwaukee's Norichika Aoki while tagging him out during a rundown Sunday. Freese was replaced by Ty Wigginton, who grew up in suburban Chula Vista. ... Marquis has a 2.27 ERA during his five-game winning streak. ... The series continues Tuesday night when St. Louis RHP Adam Wainwright (5-3, 2.51 ERA) faces RHP Edinson Volquez (3-4, 5.55).