The Padres backed Kennedy with some rare run support.
"He deserved that one," Padres manager Bud Black said. "He's been a victim of not a lot of runs and if you look across the board at his numbers, all that stuff, he's been good. We just haven't scored for him and I'm glad we got it done in the bottom half of the sixth."
It appeared Kennedy was headed for another tough-luck loss. He was trailing 1-0 when he left for a pinch-hitter in the sixth.
The Padres scored four times in the inning, surprising Chicago starter Jason Hammel (5-3).
"I felt in complete command," Hammel said. "I felt like I was going to go complete-game shutout. Everything was working."
Chase Headley tied it with a sacrifice fly and the Padres went ahead 2-1 Carlos Quentin's pinch-hit single off reliever James Russell. Two walks by Hammel helped extend the inning.
For Quentin, it was his third pinch-hit RBI in two games after a two-run, homer in Saturday's loss.
"We were going to stay away a little bit from Quentin," Cubs manager Rick Renteria said. "The ball just came back out over the plate."
Jedd Gyorko added an RBI double and when center fielder Emilio Bonifacio misplayed the ball for an error, pinch-runner Tyson Ross also scored for a 4-1 lead.
Ross, a pitcher, ran for Quentin and scored a run for the first time in the majors. He slid home, although there was no throw to the plate.
"I figured better safe than sorry," Ross said.
A sixth-inning home run by Junior Lake gave the Cubs a brief lead, although it took a little while for him to celebrate.
Lake hit an arching drive to left field and Seth Smith appeared as if he caught the ball before it reached the seats. A disappointed Lake nearly veered off the basepaths, but he resumed his trot third when umpire Greg Gibson gave the home run signal.
Hammel retired 11 straight before Yonder Alonso lined a single in the fifth inning for the Padres' first hit. Alonso stole second and advanced to third on Cameron Maybin's one-out infield single. But Maybin was picked off first by Hammel and Rene Rivera struck out to end the threat.
The Cubs didn't have much luck against Kennedy early. Castro got into scoring position in the second inning after a leadoff single and a walk, but Kennedy got the next three batters.
Hammel pitched 5 2-3 innings, allowing three runs on three hits and two walks, with five strikeouts.
But this day belonged to Kennedy, and that it came at Petco Park made all the better.
"It's always great to see runs scored like that," Kennedy said, "whether you're pitching or not."
NOTES: The Padres are encouraged with the progress RHP Andrew Cashner is making with his sore right elbow. Cashner will throw again on Monday after playing catch on Saturday. ... Padres LHP Robbie Erlin, on the DL with a sore throwing elbow, is scheduled to throw next weekend ... Quentin is expected to start on Monday against the Diamondbacks. Quentin had missed four games with a groin injury. ... Luis Valbuena's eight-game hitting streak for the Cubs, which tied a career high, was snapped. ... Cubs RHP Jeff Samardzija (0-4, 1.96) faces Giants RHP Yusmeiro Petit (3-1, 4.76) on Monday. It will be Samardzija's 200th career game. ... Ross (5-4, 2.64) goes against Arizona RHP Brandon McCarthy (1-6, 4.67) on Monday.