The 26-year-old left-hander, who started 25 games for the Augusta GreenJackets in 2005, returned to the rotation after a nearly three-week demotion to the bullpen. He only got the call because 303-game winner Randy Johnson went on the disabled list this week with a shoulder injury.
Gold Glove center fielder Aaron Rowand saved the no-hitter with a leaping catch at the center-field fence to rob pinch-hitter Edgar Gonzalez for the second out of the ninth inning.
Sanchez (3-8) nearly tossed a perfect game the only runner the Padres managed came on an error by third baseman Juan Uribe in the eighth.
With his father cheering from the stands, Sanchez threw a called third strike past Everth Cabrera to end it and thrust his arms in the air after his first career complete game. The pitcher was quickly mobbed by teammates, including Johnson the last to throw a perfect game.
Sanchez said his father arrived in San Francisco the previous night. When the pitcher came off the field, his dad was among those waiting in the dugout to congratulate him.
"This is the first time he has seen me pitch. This is a gift for him," said Sanchez, who struck out 11. "I feel awesome."
It was the Giants' 13th no-hitter and first since John Montefusco did it on Sept. 29, 1976, at Atlanta. It was their first no-hitter in San Francisco since Ed Halicki beat the New York Mets in the second game of a doubleheader on Aug. 24, 1975.
The Padres failed to get a hit for the first time since Bud Smith blanked them 4-0 pitching for St. Louis on Sept. 3, 2001, and the seventh occasion in franchise history.
Sanchez did it on 110 pitches, 77 for strikes. After the final one, catcher Eli Whiteside came rushing with a hug, followed moments later by all their teammates. The Big Unit himself was quick to congratulate his fellow southpaw.
Sanchez had a five-start winless stretch earlier this season in which he went 0-4. He told The Associated Press two days earlier that he hadn't lost his confidence in his ability to pitch and be a starter in the major leagues and manager Bruce Bochy hadn't lost faith, either.
"I want to be a starter. They gave me a second chance, you see what happened tonight," Sanchez said.
Sanchez pitched the first no-hitter in the majors since Carlos Zambrano for the Chicago Cubs against the Houston Astros in Milwaukee on Sept. 14, 2008. That game was relocated from Houston to Miller Park because of Hurricane Ike.
His father and brother stood nervously with the rest of the crowd of 30,298 at AT&T Park on a cool night in the Bay Area and his dad couldn't look at the end. But Sanchez's family quickly got down to the celebratory dugout to congratulate a pitcher who made his 14th start of the season the most special of his career after months of struggles.
Cabrera, the last batter of the game, squared to bunt on the first pitch bringing a chorus of boos from the crowd. Sanchez then froze Cabrera with a breaking ball, setting a career-high with his 11th strikeout. Cabrera protested the call, looking at plate umpire Brian Runge in disbelief.
Bochy greeted Sanchez near the third base line, followed by a stream of teammates and coaches who shook hands and hugged the hard-throwing lefty.
The celebration continued into the dugout as fans remained standing and cheering. Sanchez's father greeted his son in the dugout and the two shared a long embrace before Sanchez jogged back onto the field and tipped his cap to the cheering crowd.
Sanchez finished the Giants' major league-leading 13th shutout of the year, following All-Star and reigning NL Cy Young Award winner Tim Lincecum's no-hit bid into the seventh inning a night earlier against San Diego.
The last no-hitter in San Francisco was pitched by Kevin Brown of San Diego on June 10, 1997, at Candlestick Park so this was the first at the Giants' 10-year-old waterfront ballpark.
Pablo Sandoval hit a three-run homer to center off Josh Banks (1-1) in the fifth. Rowand also had three RBIs.
Uribe and Whiteside had RBI singles in a four-run second inning. Rowand added a two-run single.
Whiteside started in place of regular catcher Bengie Molina, whose wife was expecting a baby.