Manning threw for 308 yards and four touchdowns, including a 65-yarder to Reggie Wayne to go ahead for good, and the Colts beat the Jacksonville Jaguars 35-31 Thursday night to improve to 14-0 for the first time in franchise history.
The wild game on a cool night included 714 yards, 43 first downs, 10 lead changes, six punts, several big plays and just two turnovers.
"This was an old-time shootout at the OK Corral," Colts coach Jim Caldwell said.
Jacksonville had a chance to win it in the closing minutes, but David Garrard overthrew Mike Thomas on a third-and-10 play with about a minute to play. Jacob Lacey intercepted the ball, and the Colts ran out the clock.
Indianapolis extended its NFL-record winning streak in the regular season to 23 and became the third 14-0 team in league history, joining the 1972 Miami Dolphins and 2007 New England Patriots. New Orleans can join the list with a victory over the Dallas Cowboys on Saturday night.
"This is who we are," Wayne said. "We're built for 60 minutes. It won't be pretty all the time, but we're getting it done."
The Jaguars (7-7) lost for the third time in four games and no longer controls their fate in the AFC wild-card race.
"We were close, so close, to being in this locker room celebrating," cornerback Derek Cox said. "But there's no moral victories. It's about winning ... It's not in our hands anymore. But we still have two games left."
They have Manning to thank for the latest setback, which spoiled the team's only home game not blacked out on local television this season.
He completed his first 13 passes and was nearly as efficient as he was in last year's game in Jacksonville, when he completed 17 in a row.
Manning finished 23 of 30, picking apart Jacksonville's secondary early and often. His only real mistake wasn't even his fault. Dallas Clark bobbled a pass that Reggie Nelson tipped and Daryl Smith intercepted in the third quarter. The Jaguars turned the error into a touchdown and a 24-21 lead.
But it was short-lived.
Manning answered with an 80-yard drive, hitting Wayne with consecutive passes and later finding Clark across the middle for a 27-yard score. Wayne caught five passes for 132 yards. Clark had seven receptions for 95 yards and two scores.
Special teams chipped in, too. Chad Simpson returned a second-quarter kickoff 93 yards for a touchdown to put Indy ahead 14-10.
The Jaguars, who have lost eight of 10 in the series, ended up in a shootout with Manning & Co. -- a huge mistake for a team built to run the ball and take advantage of play-action passes.
Garrard was 23 of 40 for 223 yards and three touchdowns. Maurice Jones-Drew ran 27 times for 110 yards and a score, and caught five passes for 30 yards and a touchdown. But once the Jaguars got behind and abandoned the running game, they had trouble sustaining drives.
It might have been worse had defensive ends Dwight Freeney and Robert Mathis played extensively. Caldwell kept both players on the bench most of the night for precautionary reasons. There had been talk all week about Caldwell resting some key players since his team already has a first-round bye and home-field advantage locked up throughout the AFC playoffs.
But Manning, Wayne, Clark and other stars played the whole game.
They did most of the damage, too.
The dagger came with 5:23 remaining, when Manning found Wayne streaking down the sideline for the 65-yarder. Safety Reggie Nelson seemed to bite on a pump fake, allowing Wayne to get behind the coverage.
"What a huge play when we needed it," Manning said. "He's a great player. He comes to play. We haven't gotten him the ball recently as much as we'd like, but he draws a lot of attention and you still want to get him the ball. His presence allows us to get other guys open."
It was the biggest play in a second half that didn't quite live up to the opening 30 minutes.
The first half was a back-and-forth affair that included 336 yards, 57 plays, 38 points, 23 first downs, one penalty, no turnovers and not a single punt. The half took a little more than an hour to play, so fast that the league's broadcast representative spent the final few minutes scrambling to plug in all the TV timeouts.
Manning was perfect, completing 12 of 12 passes for 116 yards and had touchdown passes to Clark and Austin Collie. Clark made a sliding grab in the back of the end zone for a 6-yard score and a 7-3 lead early in the second quarter. Collie's catch, a 23-yarder on a seam route that he briefly bobbled at the goal line, put Indy ahead 21-17 with 35 seconds remaining.
"We knew they were going to put up points," Jaguars receiver Mike Sims-Walker said. "I was saying all game, 'It's going to be a shootout.' They score, we score. We always play them tough. Obviously, we didn't do a good enough job."
Manning's four-TD game was the 21st of his career, tying him with Dan Marino for second in NFL history. Manning now has 10 4,000-yard seasons, most ever. ... Colts PK Matt Stover became the fifth player in NFL history with 2,000 career points. ... Colts DE Keyunta Dawson injured a knee in the second quarter and did not return. ... Jones-Drew broke the franchise record with his 15th rushing TD of the season. Fred Taylor had 14 in 1998. ... There was a moment of silence before the game to honor Chris Henry, the Cincinnati Bengals wide receiver who died Thursday from injuries after he fell out of the back of a moving pickup truck driven by his fiancee.