Luck took advantage of a pair of penalties by San Francisco to open Indianapolis' seven-play, 80-yard scoring drive over the opening 3:40 for a 7-0 lead.
On the Colts' first play from scrimmage, safety Donte Whitner received a 15-yard unnecessary roughness penalty when he led with his helmet on a hit against Bradshaw after a 3-yard catch. Tarell Brown was flagged for pass interference on the next play.
Another penalty on Brown, for holding, gave the Colts a first down at the 23 midway through the second quarter and set up Vinatieri's 43-yard field goal. He kicked a 41-yarder in the third quarter.
Brown was penalized yet again for pass interference midway through the fourth.
Luck kept drives going with clutch plays as the Colts won the third straight meeting with San Francisco.
On third-and-9 and throwing from near his end zone late in the third, Luck hit Reggie Wayne for a 25-yard gain in which Wayne broke through several tackle attempts.
All-Pro linebacker Patrick Willis went down on the play and was helped off the field moments later with a groin injury that sidelined him for the rest of the game.
The Colts busted through San Francisco's defensive line, which lost nose tackle Ian Williams to a season-ending ankle injury last week.
"It's one of those games you look back on down the road and say, 'This was a signature win, maybe one that helped you to do great things, that helped you accomplish the program you built," Pagano said.
Notes: 49ers special teams standout Bubba Ventrone left after the first quarter with a concussion. ... San Francisco TE Vernon Davis' streak of 98 straight games played was snapped. ... The 49ers had their regular-season winning streak vs. AFC opponents end at five. ... Gore has 2,687 career yards receiving, moving into second place in franchise history for a RB behind Roger Craig (4,442).
AP NFL website: www.pro32.ap.org
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