Sandoval is the fourth player to hit three home runs in a World Series game, after Albert Pujols last year, Reggie Jackson in 1977 and Babe Ruth, who did it in 1926 and 1928.
Of those, Sandoval is the only one to homer in his first three at-bats of the game.
Sandoval added a single in the seventh inning to improve to 4-for-4 on the night.
In the first inning, Sandoval connected on a high 95 mph pitch with an 0-2 count and sent the ball just over the wall in right-center. Then, on the 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!"
In July, Sandoval hit the first bases-loaded triple in All-Star Game history off Verlander, the reigning AL MVP and Cy Young Award winner.
Sandoval's third homer was a solo shot to center field with one out and nobody on in the fifth.
Sandoval is the 10th player in major league history to hit two or more home runs in the first game of the World Series. He has an RBI in six straight postseason games, breaking the team record for longest streak that he previously shared with Barry Bonds.
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 2001. The last three-homer game by a Giant was Aubrey Huff at St. Louis in June 2011.
Information from The Associated Press was used in this report.