In the 13th meeting between the star quarterbacks, and first since Manning joined the Denver Broncos, Brady directed four scoring marches of at least 80 yards and the Patriots won 31-21 on Sunday.
Brady improved to 9-4 against Manning, who left the Indianapolis Colts after last season. Brady completed 23 of 31 passes for 223 yards and one touchdown and ran for another. Manning was 31 of 44 for 345 yards and three touchdowns but lost a fumble on a third-quarter sack.
The fumble led to Stevan Ridley's 8-yard run that put the Patriots (3-2) ahead 31-7 with about five minutes left in the third quarter. Ridley led the Patriots with a career-high 151 yards rushing.
Manning then threw touchdown passes of 2 yards to Eric Decker and 5 yards to Brandon Stokley but Denver (2-3) lost a fumble with 3:42 remaining.
The Patriots set a franchise record with 35 first downs as they kept their offense rolling one week after gaining 580 yards, 247 on the ground, in a 52-28 rout of the Buffalo Bills. The Broncos sputtered after beating the Oakland Raiders 37-6.
Brady and Manning first faced each other in the third game of the 2001 season. The Patriots won 44-13 in Brady's first career start.
There were plenty of close games in subsequent regular-season matchups with six of the previous seven decided by seven points or less. Sunday's outcome was different, although Manning brought the Broncos back from a 24-point deficit in the second half.
His scoring pass to Stokley followed a fumble by Brady on a sack.
Ridley then lost a fumble on New England's next possession and Manning seemed poise to keep the comeback going. A 28-yard completion to Demaryius Thomas put the ball at the Patriots 14 but two plays later Willis McGahee fumbled and Jermaine Cunningham recovered at the New England 11..
The Patriots led 17-7 at halftime and 31-7 after three quarters. Brady and his runners kept slicing through the Denver defense with a balanced attack. They went ahead to stay, 14-7, midway through the second quarter on a 14-play drive (seven pass plays and seven runs) capped by Shane Vereen's 1-yard run.
Ridley had his third 100-yard rushing game of his career, all this season. Wes Welker, the NFL's leading receiver last year with 122 catches, had 13 for 104 yards.
The Broncos wasted an excellent opportunity on their first series. Manning hit Thomas with a 43-yard completion to the Patriots 10-yard line, but Sterling Moore stripped the ball and recovered the fumble. The Patriots went four-and-out on the ensuing possession then the Patriots scored on their next three possessions -- 84 yards to Brady's 8-yard pass to Welker, 80 yards to Vereen's touchdown and 93 yards to Stephen Gostkowski's 23-yard field goal.
Denver did tie the game 7-7 on Manning's 1-yard pass to Joel Dreessen but didn't reach the end zone again until Manning hit Decker to end a 90-yard march, cutting the lead to 31-14 with 1:08 left in the third.
The Patriot even got key plays from their backup running backs. Brandon Bolden had a 24-yard gain on the series leading to Gostkowski's field goal. On that same drive, Danny Woodhead gained 25 yards on a pass from Brady on a third-and-14 play from the Broncos 11.
Woodhead kept another drive going in the third quarter with a 19-yard rush on third-and-17 at the Patriots 43. That series ended with Brady's touchdown dive.
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