ST. LOUIS -- When San Diego Padres interim manager Pat Murphy sent up Will Venable to pinch-hit for pitcher Shawn Kelley in the top of the 11th inning Thursday night, he didn't know how poorly Venable had performed in that role this year.

As Murphy admitted after the game, he was glad he didn't know.

Jumping on the first pitch, Venable cracked a tie-breaking two-run homer to give San Diego a 5-3 win over the St. Louis Cardinals at sold-out Busch Stadium.

"I didn't draw it up this way," joked Murphy. "I would have rather won it in nine, but this was a great team win. I'm happy for Will."

Before Venable had the chance to improve on a sickly 1-for-17 mark as a pinch-swinger, the Padres needed a replay reversal. Shortstop Clint Barmes' two-out fly ball down the right field line was originally ruled foul by first base umpire David Rackley.

But Murphy asked for a review and the umpires on duty in New York City overturned the call as the ball plopped just inside the foul line and bounced into the seats for a ground-rule double.

Venable whaled his sixth homer of the year moments later, a 420-foot shot over the right-center field wall off Carlos Villanueva (3-3) that enabled San Diego (38-43) to start a 10-game road trip on a positive note.

"A huge team win for us," said starting pitcher Tyson Ross. "A start in the right direction."

Ross had something to do with that, and it wasn't limited to his 13th quality start in 17 outings. He blasted the first homer of his career, a 366-foot opposite field drive which barely cleared the right field wall in the fifth for a 3-1 lead.

It was the first homer for a Padre pitcher since Ian Kennedy went deep last year against Miami, and the first opposite-field blast by a San Diego hurler since Andy Benes did it on Sept. 3, 1989 against Philadelphia.

"It was cool, and it turned out to be a big run, because I gave up two right after that," Ross said.

Despite ceding the lead when he allowed an RBI single to third baseman Matt Carpenter and a run-scoring double to right fielder Jason Heyward in the Cardinals' half of the inning, Ross still lasted six innings. He gave up four hits and three runs, walking five and fanning six.

Four relievers worked five scoreless innings for San Diego, with Shawn Kelley (1-2) whiffing four in his two innings for the win. Craig Kimbrel pitched the 11th to garner his 20th save.

St. Louis (51-27) dropped three in a row at home for the first time this year despite a good start from lefty Tim Cooney. Making just his second big league appearance, Cooney gave up only four hits and three runs, two earned, in six innings. He walked two and struck out six.

The Cardinals outhit the Padres 9-8 and also drew a half-dozen walks, but were just 1-for-13 with runners in scoring position. They stranded 13 men for the game, leaving runners at first and third in the eighth, and second and third in the ninth.

Catcher Yadier Molina appeared to have a game-winning single off Kelley in the ninth with men at first and second, but first baseman Derek Norris robbed him with a full-length dive. Kelley then fanned left fielder Randal Grichuk.

"Almost a big hit with Yadi," St. Louis manager Mike Matheny said. "It was a plus defensive play to knock that down. We let those chances go, they come back to bite us."

Venable took the biggest bite of them all.

"I wanted to be ready for fastball and anything up," he said.

NOTES: St. Louis made room for Thursday night's starting pitcher, LHP Tim Cooney, by placing OF Jon Jay (left wrist) on the 15-day disabled list. Jay is batting .223 with one homer and 10 RBIs in 166 at-bats. ... San Diego 3B Yangervis Solarte, who homered in the second was tossed after the top of the sixth by home plate umpire Bob Davidson for slamming his helmet after Rackley called him out on a checked swing. ... The Cardinals signed five international players Thursday, landing 16-year-old Venezuelan RHP Alvaro Seijas for $762,500 and also inking 16-year-old SS Raffy Ozuna of the Dominican Republic for $600,000.