Despaigne became the fourth Padres pitcher to throw seven scoreless innings in his first big league start, leading San Diego to a 6-0 victory over the San Francisco Giants on Monday night.
''He pitched great didn't he?'' Padres manager Bud Black asked. ''Are you kidding me? That was great.''
Tommy Medica hit a two-run double off Matt Cain (1-6) after the umpires took away a three-run home run by Yasmani Grandal on a replay review to give the crafty Despaigne (1-0) the support he needed.
Despaigne, who defected from Cuba last summer, got the win less than two months after Byrnes signed him to a minor league deal. Byrnes was fired Sunday so he didn't get the chance to benefit from the decision.
Despaigne had a 6.03 ERA in seven minor league starts in his first season as a professional after defecting from Cuba last summer.
''It took me for surprise to be here,'' he said through an interpreter. ''It was a dream come true.''
Despaigne kept the Giants off-balance all game by changing his arm angle and mixing in big, slow curveballs with his harder pitches. He allowed four hits and became the seventh pitcher in the past 100 years to throw at least seven scoreless innings with no walks in his first career start.
Despaigne had the element of surprise in his favor as the Giants had not even seen him pitch in spring training.
''At this point in the year you've kind of seen everything but he was just on,'' right fielder Hunter Pence said. ''He was locating, he had the ball moving a lot of different directions. He threw me pretty much everything. He didn't really leave too much over the plate. I think he just mixed it up the whole game.''
The Giants lost for the 10th time in 13 games.
Neither team had a hit in the first three innings before the Padres got to Cain in the fourth. The rally started when Everth Cabrera reached on a one-out infield single and advanced to third on Seth Smith's single.
One out later, Grandal hit a drive to right-center that initially appeared to clear the wall for a three-run homer. But Pence immediately signaled that a fan interfered on the play and ran toward the umpires to protest.
The umpires called for a video review and the play was changed to a double with Smith being sent back to third base even though he most likely would have scored easily from first on a two-out hit to the deepest part of the stadium.
Black ran out of the dugout to challenge the ruling and was immediately ejected by crew chief Brian O'Nora.
''I just thought the logical thing to do was have Smitty score,'' Black said. ''I was in disbelief when they placed him at third base.''
The call became moot when Medica followed with a two-run double to make it 3-0 as Cain struggled once again.
The Padres tacked on three runs in the eighth with an RBI single by Cabrera, a run-scoring double to Smith and a throwing error by Pence.
Cain allowed six runs and seven hits in 7 1-3 innings and has just one win in 12 starts this season.
''I've been throwing the ball good but I haven't been making the pitch that I need to here and there to shut down an inning,'' Cain said. ''I need to do a better job of doing that. I think everything else will work itself out but I've got to make those pitches.''
NOTES: There was a pregame video tribute to Padres Hall of Famer Tony Gwynn, who died last week at age 54. There was also a No. 19 honoring Gwynn on the wall in right field. ... Padres 3B Chase Headley (back) missed his fourth straight game but could return Tuesday. ... Giants OF Angel Pagan (back) missed his seventh straight game. ... Giants INF Marco Scutaro (back) is scheduled to play three innings on a rehab assignment in the Arizona League on Tuesday. ... Tim Hudson (4-2) starts the second game of the series for San Francisco against Jesse Hahn (2-1).