His second walk-off hit in two weeks gave the Phillies consecutive wins for the first time since a three-game streak May 17-20.
"It's what you play the game for, it's what you dream of as a kid," Brignac said.
Brignac had a game-winning RBI single in the 14th inning of a 6-5 win over the New York Mets on May 30.
His only other walk-off hit before this year was a solo homer for Tampa Bay off Yankees reliever Sergio Mitre in the 11th inning on Sept. 13, 2010. That gave the Rays a 1-0 win and put them a half-game ahead of New York in the AL East.
Starters Cole Hamels and Tyson Ross matched zeroes, but didn't get decisions. Hamels struck out a season-high 11 and allowed five hits in eight shutout innings for the Phillies. Ross struck out seven in seven scoreless innings, giving up four hits.
"Cole was outstanding," manager Ryne Sandberg said. "Real sharp with his command, his fastballs and change-ups. He's looking real good."
Nick Vincent (0-2) walked Domonic Brown with one out and hit Carlos Ruiz on 1-2 pitch. Brignac then sent a 2-0 pitch into the right-field seats for his first homer with the Phillies. Brignac was just 8 for 40 with 19 strikeouts before going deep.
Brignac pointed into the dugout as he jogged to first, slapped his hands together after rounding the bag and was mobbed at the plate by jubilant teammates. He got doused with shaving cream afterward by A.J. Burnett.
"It feels great to come through for my teammates," Brignac said. "Cole pitched great."
Jimmy Rollins stole two bases on the same pitch in the Phillies first after moving within three hits of breaking Mike Schmidt's franchise record of 2,234.
Rollins lined a one-out single to right, but jogged slowly to first and was grimacing in pain. He appeared hobbled perhaps because he hit a foul off his leg.
But Rollins then stole second base, diving headfirst ahead of the throw. He got up, saw no one covering third base because of an overshift on Ryan Howard and swiped that bag. Howard walked, but Marlon Byrd struck out to end the inning.
Johnny Damon once did the same thing against the Phillies, stealing second and third in the ninth inning in Game 4 of the 2009 World Series, a 7-4 win for the Yankees.
Hamels pitched out of a couple jams in the early innings. Cameron Maybin led off the third with a double and advanced on Jace Peterson's sacrifice, a drag bunt attempt. But Hamels fanned Ross and retired Chris Denorfia on a grounder.
San Diego loaded the bases with two outs in the fourth, but Hamels struck out Maybin swinging to end the inning.
"I feel like I've really been able to execute start to finish," Hamels said. "I'm not giving in when I get behind in counts, not overdoing it. I'm able to make good pitches and getting good results."
The Padres, who entered with the worst batting average in the majors at .217, had just five hits and none after the fourth inning.
Carlos Quentin (1 for 29), Everth Cabrera (0 for 23) and Peterson (0 for 20) continued their slumps, going a combined 0 for 10 with six strikeouts.
"That was a great pitcher's duel," Padres manager Bud Black said. "Both guys were outstanding."
Phillies ace Cliff Lee has started throwing again, but it's uncertain when he'll return. Lee has missed four starts since landing on the disabled list with an elbow strain. ... Hamels had double-digit strikeouts for the 26th time, passing Jim Bunning for third place on the Phillies' list. ... Byrd was 0 for 4 with four strikeouts. ... Ross lowered his ERA to 2.97. ... The Phillies are 22-13 vs. the Padres at Citizens Bank Park. ... LHP Eric Stults (2-7, 5.68) goes for the Padres against RHP Kyle Kendrick (1-6, 4.30) in the series finale Thursday afternoon.
Copyright by STATS LLC and The Associated Press
PHILADELPHIA, PA - JUNE 11: Jimmy Rollins #11 of the Philadelphia Phillies winces in pain while at first base, as...
25,398 (58.2% full) - % is based on regular season capacity
68 degrees, cloudy
Home Plate - Tim Welke, First Base - Todd Tichenor, Second Base - Clint Fagan, Third Base - Tim Timmons
Opponents are 1-for-20 (.050 BA), including 10 strikeouts, in at-bats ending with Cole Hamels' curveball this season. The Padres are hitting .168 with a .439 OPS in at-bats ending with a curve this season, both of which are the worst in the major leagues.