Sandoval hit a solo home run to right-center in the first, a two-run, opposite-field drive to left in the third and another bases-empty shot into the center-field batter's eye in the fifth. He joined Babe Ruth (1926 and 1928), Reggie Jackson (1977) and Albert Pujols (2011) as the only players with three-homer games in the Series.
Barry Zito, who like Sandoval watched the 2010 Series opener from the dugout, won by allowing one run and six hits in 5 2-3 innings.
Sandoval went 4 for 4 with four RBIs, also singling in the seventh against Jose Valverde. He became the first Giants player with a three-homer game at home since Barry Bonds in August 1994 at Candlestick Park.
Verlander was chased after allowing five runs and six hits in four innings, his shortest start this year. He threw 98 pitches, and Detroit manager Jim Leyland could alter his rotation and start him in Game 4 on short rest instead of Max Scherzer. That would enable Verlander to pitch a possible Game 7, again on three days' rest.
Verlander was 0-2 as a rookie in the 2006 Series against St. Louis but had been superb this October, entering with a 3-0 record and a 0.74 ERA.
Madison Bumgarner, 0-2 with an 11.25 ERA for the Giants in two postseason outings, starts Game 2 on Thursday against Detroit's Doug Fister, who has a 1.35 ERA with no decisions in two postseason appearances this year. The Series then shifts to the Motor City for Game 3 on Saturday.
The winner of the opener has claimed the title 66 of 107 times, including eight of last nine. The NL is seeking to win three straight Series for first time since 1979-82.
Sandoval hit the first bases-loaded triple in All-Star game history off Verlander in July, and kept on going against the reigning AL MVP and Cy Young Award winner.
He connected on a high 95 mph pitch with an 0-2 count in the first inning and sent the ball just over the wall in right-center. Then, on the very next pitch after a mound visit by Tigers pitching coach Jeff Jones in the third, Sandoval hit a two-run, opposite-field drive into the seats in left for a 4-0 lead. Verlander simply said, "Wow!"
Sandoval had been benched for four of five games in the Giants' 2010 Series win over Texas when he entered in a 3-for-14 slide. The Giants then told Sandoval, nicknamed Kung Fu Panda for his roly-poly physique, to get in shape or start the next season in the minor leagues.
Winning by home run is unusual for the Giants, whose 103 home runs were last in the major leagues. The only other three-homer game at the ballpark was by the Los Angeles Dodgers' Kevin Elster in the very first opener, in 2000. The last three-homer game by a Giant was Aubrey Huff at St. Louis in June 2011.
Angel Pagan had another of the Giants' unusual postseason hits with two outs in the third when his one-hopper kicked off the corner of the third-base bag and ricocheted past Miguel Cabrera at almost a right angle into short left field. Marco Scutaro, who struck out just once in 48 at-bats during the NL playoffs, fouled off two 98 mph full-count pitches and lined a single into center field to bring up Sandoval.
Zito, dropped from the Giants' roster for the 2010 postseason after a four-year slump, finally justified the $126 million, seven-year contract the Giants gave him after the 2006 season. The 2002 AL Cy Young Award winner was helped when left fielder Gregor Blanco made neat diving grabs of liners by Cabrera in the third and Prince Fielder in the sixth. Given a 6-0 lead, Zito gave up an RBI single in the sixth to Cabrera, baseball's first Triple Crown winner in 45 years.
Jhonny Peralta hit a two-run homer for the Tigers in the ninth off mop-up reliever George Kontos.
Zito added an opposite-field RBI single to left in the fourth. After getting just four hits during the regular season, Zito has singles in consecutive postseason appearances.
Tim Lincecum, who won twice in the 2010 Series, came out of the bullpen with two on and two outs in the sixth and struck out Jhonny Peralta. The two-time Cy Young winner retired seven in a row, striking out five.
Scutaro and NL batting champion Buster Posey added RBI singles in the seventh against Valverde, pitching for the first time since allowing a pair of two-run homers in the ninth inning of the AL championship series opener. Valverde's postseason ERA this year rose to 30.38.
Coming off its first AL pennant since 2006, Detroit had nearly a week off after sweeping the New York Yankees in the AL championship series. San Francisco had just a day to rest after overcoming a 3-1 deficit against defending champion St. Louis in the NLCS.
Detroit had just the seventh-best record in the 14-team AL at 88-74, and no previous World Series team had been lower than fifth, according to STATS LLC. San Francisco was tied for third in the NL at 94-68.
Back in San Francisco's bayside ballpark for the second time in three years, the World Series took on the Giants' Halloween colors of orange and black as fans waved towels and pompons. The Grateful Dead's "I Will Survive" and "Friend of the Devil" were among the songs played as the Tigers took batting practice.
Renel Brooks-Moon, who in 2002 became the first woman to be serve as public-address announcer for a Series game, skipped over Detroit's reserves during the pregame introductions.
Hall of Famers Willie Mays, Willie McCovey, Gaylord Perry and Orlando Cepeda were on the field for the ceremonial first pitch - thrown by Perry.
Detroit also brought along some baseball royalty in Hall of Famer Al Kaline, a team adviser.
Seeking their first World Series title since 1984, the Tigers helped create the first title matchup between teams from the AL Central and NL West.
NOTES: This was the Giants' 50th World Series win. ... The team hosting the first two games has won 21 of the last 26 World Series: the exceptions were Toronto (1992), the Yankees (1999), Florida (2003), St. Louis (2006) and Philadelphia (2008). ... Cabrera became the fourth player to appear in the Series in the year he won the Triple Crown, joining Mickey Mantle (1956), Frank Robinson (1966) and Carl Yastrzemski (1967). ... Delmon Young hit into only the second 2-4 double play in postseason play, with Fielder tagged out at second. The other was on a bunt by the Boston Braves' Sibby Sistsy in Game 6 of the 1948 World Series, STATS said. ... Sandoval became only the fifth player to homer twice off Verlander in the same game, joining Oakland's Nick Swisher (2006), Carlos Quentin of the Chicago White Sox (2011), Cleveland's Shelley Duncan (2001) and Tampa Bay's Desmond Jennings (June 29).