The Giants used a 32-yard Hakeem Nicks touchdown reception to get within seven, 27-20, midway through the final period. The visitors then forced the 49ers to punt before marching down the field. Faced with a 4th-and-2 from the 10 with 37 seconds to play, Smith put his arms up to knock down Manning's pass.
Alex Smith took a few kneel downs to seal San Francisco's seventh straight victory, the club's best run since it ripped off 11 straight victories during the 1997 season.
The 49ers (8-1) got the win despite running back Frank Gore having zero rushing yards on six carries. Gore came into the game with a franchise-record five straight 100-yard efforts on the ground, but was held out in the second half due to ankle and knee injuries.