DENVER — Tom Brady lost yet another one of his trusted targets and this time he also lost a game.
C.J. Anderson scored on a 48-yard run with 12:32 left in overtime, powering the Denver Broncos past the New England Patriots 30-24 on a snowy Sunday night.
Watching from the cozy indoors at field level was Peyton Manning as Brock Osweiler and the Broncos (10-2) overcame a 21-7 fourth-quarter deficit and handed the Patriots (11-1) their first loss since 2014.
"It didn't look good at times," Broncos coach Gary Kubiak said, "but we figured out a way to get it done."
Now, the Carolina Panthers (11-0) are the NFL's only remaining unbeaten team.
Osweiler threw a 3-yard touchdown pass to Bubba Caldwell with 1:09 left in regulation to put the Broncos up 24-21. But Brady, playing without injured star tight end Rob Gronkowski, needed just five plays to drive the Patriots 51 yards and into range for Stephen Gostkowski's 47-yard field goal that tied it at the end of regulation.
New England won the coin toss and elected to receive, but thanks to a sack by Von Miller, Denver forced a three-and-out. Then, on third-and-1 from the New England 48, Anderson raced around the left sideline and into the north end zone.
Gronkowski injured his right knee with 2:49 left in regulation and was carted off. There was no immediate word on his status.
Anderson rushed for 113 yards and two TDs on 15 carries.
Overall, the Broncos ran for 179 yards, particularly impressive given their two-touchdown deficit for much of the first half and their 21-7 hole they found themselves in after Brady threw a 63-yard scoring pass to Brandon Bolden on the first play of the fourth quarter.
The Patriots managed just 39 yards on 16 carries, however.
Osweiler improved to 2-0 since taking over for Manning. He completed 23 of 42 passes for 270 yards with one TD and one interception. Brady also was 23 of 42 for 280 yards with three TDs and no interceptions. Both were sacked three times.
Brady's three TD tosses put him in a tie with Dan Marino for third on the career list. But with Manning sitting this one out in a walking cast on his left foot, the greatest quarterback rivalry was put on hold — perhaps forever.
Instead of a 17th meeting between the QB greats, it was Brady versus Osweiler, which doesn't have the same Hall of Fame ring to it.
It still had plenty of panache.
Demaryius Thomas, who didn't catch any of the first 11 balls thrown his way, hauled in a 36-yard pass to midfield just before the 2-minute warning and Osweiler hit Emmanuel Sanders for 39 yards to the 8 before finding Caldwell in the end zone to give Denver its first lead of the night.
Things looked bleak after Bolden's TD made it 21-7 and New England's defense forced a punt. But Chris Harper muffed the punt and Shaq Barrett recovered for Denver at the Patriots 36.
That led to Anderson's 15-yard TD run.
The Broncos again drove downfield and reached the New England 3, but they settled for Brandon McManus's 21-yard field goal with 6:08 left to make it 21-17.
Both teams went three-and-out and the Patriots were moving downfield when Gronkowski got hurt.
He was carted off with 2:49 left after injuring his right knee on an incompletion when safety Darian Stewart sliced across his body and hit his right knee — a clean hit.
Star pass rusher DeMarcus Ware missed the game with a bad back and Denver lost two more members of the league's top-ranked defense on one play in the first quarter. Pro Bowl safety T.J. Ward and nose tackle Sylvester Williams suffered ankle injuries on New England's first run when LaGarrette Blount managed 2 yards. Ward and Williams were in walking boots after the game.
Neither returned, nor did right guard Louis Vasquez (groin), who went out in the second quarter.
Without receivers Julian Edelman (foot), Danny Amendola (knee) and Aaron Dobson, who went on injured reserve last week with an ankle injury, Brady relied on his big tight ends.
He hit Gronkowski from 23 yards out and Scott Chandler from 9 yards for a 14-0 lead. Gronkowski, who was held to two harmless catches against Buffalo last week, was single covered and easily scored when safety Darian Stewart went for the swipe instead of the tackle.
Chandler sped past Miller in coverage and scored easily when safety David Bruton Jr. was slow to slide over.
Gronkowski's TD followed a 25-yard punt that gave Brady's banged-up bunch great field position at the Denver 47, and Chandler's came after Chandler Jones' interception at the Denver 15.
Denver cut the deficit to 14-7 at the half on Ronnie Hillman's 19-yard TD run with 2:07 left in the second quarter. It came one play after linebacker Dont'a Hightower hobbled off with a knee injury.
"After Ronnie's first touchdown, he came to me and said, 'Now, you're going to grind it out and get all the glory,"' Anderson said.
Follow AP Pro Football Writer Arnie Melendrez Stapleton on Twitter: http://twitter.com/arniestapleton