Pedroia had brought back memories of Carlton Fisk's 1975 Game 6-winning home run, sending a first-inning drive about 10 feet foul of the Green Monster foul pole — and waving his left arm once to try to urge the ball fair as he came out of the batter's box.
Lackey escaped a two-on, none-out jam in the second when he retired Matt Adams and David Freese on flyouts and, after a wild pitch, struck out Jon Jay.
Boston wasted a similar threat in the bottom half, then went ahead on the third.
Jacoby Ellsbury singled leading off and went to second on Pedroia's grounder. Ortiz was intentionally walked, Napoli struck out and Gomes was hit above the left elbow with a pitch, loading the bases.
Victorino, wearing red, white and blue spikes with an American flag motif, had been 0 for 10 in the Series and missed the previous two games with a bad back.
Dropped from second to sixth in the batting order, he took two balls and a called strike, then turned on a 93 mph fastball and sent it high off the Green Monster, the 37-foot-high wall in left. Gomes slid home as Yadier Molina took Matt Holliday's one-hop throw and applied the tag, then argued with plate umpire Jim Joyce.
Victorino, pumped with emotion, went to third on the throw and pounded his chest with both fists three times.
After Drew's homer, Lance Lynn relieved Wacha with two on, and RBI singles by Napoli and Victorino boosted Boston's lead to 6-0. Wacha entered 4-0 with a 1.00 ERA in his postseason career but gave up six runs, five hits and four walks in 3 2-3 innings, the shortest start of the 22-year-old's big league career.
Boston was a 30-1 underdog to win the World Series last winter but joined the 1991 Minnesota Twins as the only teams to win titles one season after finishing in last place. Now, the Red Sox will raise another championship flag before their home opener next season April 4 against Milwaukee.