Boston's Josh Beckett improved to 4-0 in the playoffs, giving up a run on six hits with nine strikeouts over seven innings.
But it was the long procession of two-out Boston hits that turned the game into a rout as Colorado, making its World Series debut, lost for the first time in 10 games and for only the second time in 23 contests.
The Red Sox had 11 hits and scored 11 times after two were away. Three of those runs came on consecutive bases-loaded walks during a seven-run fifth inning. The 12-run victory margin was the largest ever in a World Series opener.
Colorado starter Jeff Francis surrendered six runs on 10 hits in four innings. Rain fell off and on during the contest while temperatures were stuck in the low 50s.
Curt Schilling will start for Boston in Game 2 Thursday night. Ubando Jimenez will pitch for the Rockies.