The Cuban defector combined with three relievers on a three-hitter to lead San Diego to a 5-0 victory against the Giants on Friday night.
The Giants dropped to 3½ games behind the Los Angeles Dodgers in the NL West race. San Francisco's lead in the wild-card race was trimmed to one over Pittsburgh, but the Giants' magic number to clinch a wild-card spot dropped to four.
"Every time I face a team like the Giants with a pretty good lineup, I have to bring my best game into it," Despaigne said through a translator. "They have so many good hitters in the lineup that I can't afford to make too many mistakes. I have a pretty good idea of how to pitch to those guys. I have to make sure I bring my 'A' game."
The Giants had only three base runners in seven innings against Despaigne (4-7). He walked Angel Pagan opening the game and retired the next nine batters before allowing Joe Panik's double just inside first base leading off the fourth. Despaigne retired the next eight batters before Panik singled to left with two outs in the sixth. Despaigne struck out six and walked one.
Despaigne is 2-0 with a 0.45 ERA in three starts against the Giants.
"I think with him especially, I think he treats every game the same," Padres manager Bud Black said. "I don't think he pitches any different against the Giants than against any other team.
"This guy has got some savvy, he's got some guile. He's not wet behind the ears even though he's a rookie by our standards in the States. He pitched a very good game against a very good lineup."
Tim Hudson (9-12) lost his third straight start, guaranteeing the first losing record in his 16-year big league career.
He allowed five runs, four earned, on seven hits in 4 1-3 innings, with two strikeouts and two walks.
It wasn't as bad as Saturday night, when Hudson had the worst start of his career, lasting just one inning plus two batters in a 17-0 home loss to the Dodgers. He allowed six runs and eight hits while making 35 pitches.
Hudson got into trouble right away Friday when he loaded the bases with one in the Padres' first, allowing singles by Yangervis Solarte and Jedd Gyorko, and walking Yasmani Grandal. Hudson got Seth Smith to fly out to right, but Alex Amarista hit a two-run double into the gap in right-center. Cameron Maybin hit a two-run single to center before he was caught stealing to end the inning.
The Padres added an unearned run in the third when Gyorko reached on a two-base throwing error by third baseman Pablo Sandoval and scored on Smith's double to right.
The Padres recorded their ninth shutout of the season and third against the Giants. It is the most for the Padres against any opponent this season.
Since the All-Star break the Padres are 20-7 at home, the best mark in the NL.
Giants: Pagan was back in the lineup after missing three straight games with a bulging disc in his back that was irritating a nerve. He left the game after striking out in the sixth after his back tightened up.
Padres: Black said closer Joaquin Benoit is available again after not having pitched since Aug. 26 due to a sore right shoulder.
Giants: RHP Yusmeiro Petit 5-4, 3.64 ERA), who took Tim Lincecum's spot in the rotation, is scheduled to start Saturday night as he tries to bounce back from a loss to the Dodgers.
Padres: RHP Andrew Cashner (4-7, 2.20) is 2-1 with 1.85 ERA in five starts since returning from the disabled list on Aug. 23.