Manning threw three touchdown passes in the second half and Tony Carter and Chris Harris scored off turnovers by Philip Rivers as the Denver Broncos overcame a 24-0 halftime deficit to stun the San Diego Chargers 35-24 on Monday night.
Manning was 13 of 14 for 167 yards in the second half for the Broncos (3-3) who tied the Chargers (3-3) atop the AFC West.
It tied for the fourth-greatest regular-season comeback in NFL history.
"It sure was special considering what was on the line," said Manning, a four-time NFL MVP and one-time Super Bowl winner who's in his first season with the Broncos.
Manning had been 1-5 in his last six games against San Diego, all with Indianapolis.
Rivers was intercepted four times - three in the fourth quarter - and lost two fumbles. A week earlier, the Chargers blew a 10-point lead in the third quarter in a 31-24 loss at New Orleans.
"When you lose it's rough, especially in a game where you had a big lead and so much at stake," Rivers said.
The Broncos seemed finished after a nightmarish first half in which Manning served up an 80-yard interception return for a touchdown by Quentin Jammer and two special teams fumbles led to 10 points for the Chargers.
"I thought we had a good plan. It was so disappointing to have these special team mistakes," Manning said.
Manning began the comeback when he hit Demaryius Thomas on a 29-yard touchdown pass on the opening drive of the second half.
On the ensuing San Diego possession, Elvis Dumervil stripped the ball from Rivers and Carter ran 65 yards for a touchdown, holding up the ball in celebration as he approached the end zone.
Denver then sacked Rivers to force a punt and Manning capped the next drive with a 7-yard touchdown pass to Eric Decker to pull to 24-21.
Manning's 21-yard touchdown pass to Brandon Stokley gave Denver its first lead of the game, 28-24 with 9:03 left. Stokley outleaped defensive back Marcus Gilchrist to catch the ball, and then got both feet down before tumbling out of the end zone.
That score was set up by Carter's interception.
Harris sealed the victory with a 46-yard interception return for a touchdown with 2:05 left. It was his second pick of the game.
Manning finished 24 of 30 for 309 yards with one interception.
Quentin Jammer intercepted Manning and returned it 80 yards for his first career touchdown, and Antonio Gates caught his second TD pass of the game in the second quarter, extending the Chargers' lead to 24-0.
Before Jammer's TD, the Broncos appeared on their way to their first score of the game with Manning's 55-yard pass to a wide-open Decker. But Decker tripped himself at the Chargers' 40, got up and was tackled at the 30-yard line.
Manning clapped both hands to his helmet in disbelief, one of several times the star quarterback expressed frustration.
"Those kind of plays happen," Manning said. "You do kind of wonder, is this not meant to happen? Obviously Decker was sick about it.
"It's about playing 60 minutes. There's no quit in this team."
Three plays later, Manning threw a pass straight to Jammer.
Rivers was 25 of 41 for 242 yards.