Updated 2:45 a.m. ET
INDIANAPOLIS Peyton Manning failed Sunday night in his first game against his former team.
All the 37-year-old ex-Indianapolis Colts quarterback can do now is hope for a second chance.
On a night when second-year quarterback Andrew Luck, Manning's successor in Indianapolis, threw for three touchdowns and ran for another, the Denver Broncos committed four turnovers and lost for the first time this season, 39-33.
"This is a game we need to learn from," Manning said. "We, I guess, had four turnovers and still somehow had a chance to win that game. I would have liked to have seen it go to a two-point game down there toward the end and see what would have happened, but it never quite got to that point. We certainly have to improve from this game, because we weren't as sharp, execution-wise, as we'd like to be."
"It's not real fun watching him," Luck said of Manning. "But he is something to watch."
"Manning did Sunday night what he has done all season, doing it ugly without great arm strength or even great spirals, but putting the ball in spots where only teammates could catch it and run with it," writes CBSSports.com national columnist Gregg Doyel. "He completed 29 of 49 passes for 386 yards and three touchdowns.
"But he didn't win this game, in part because of a harassing Colts defense that did to him what it has done to quarterbacks for years, and in part because of the guy who replaced Manning (Luck)."
The game certainly showed how vulnerable the Broncos (6-1) are at the moment.
Already playing without their starting left tackle and center, they juggled the offensive line again. This time, Manning was hit 10 times, sacked four times, lost a fumble and threw an interception - the last two when his arm was hit before he could get rid of the ball cleanly.
Running back Ronnie Hillman was stripped of the ball inside the Colts' 5-yard line late in the game on a series when the Broncos were down two scores.
Cornerback Champ Bailey, who had just returned to the lineup last week after missing the first five games with a left foot injury, departed in the first half after hurting the same foot. Coach John Fox didn't provide an update on the severity of the injury after the game.
Without Bailey, Luck managed to extend the lead and kept the pressure on Manning all game.
And dynamic kick returner Trindon Holliday fumbled twice, losing one that led to an Indianapolis (5-2) touchdown.
Heading into the game, Manning and Denver looked virtually unbeatable. The Broncos were scoring points by the dozens in the midst of a 17-game regular-season winning streak and showed no signs of even hitting a speed bump.
But nothing went right and now the Kansas City Chiefs are the NFL's lone unbeaten team.
"That's a big play any time you give them a safety or give them the ball again," Manning said, referring to Robert Mathis' strip sack in the second quarter. "Robert's a great player, no doubt, but that was one of a number of plays that we gave them points and it was ultimately too much to overcome."
While Manning finished with solid numbers, 29 of 49 for 386 yards with three TD passes, he certainly wasn't himself. Passes fluttered, passes sailed, passes were broken up.
Luck was 21 of 38 for 228 yards with three scores and no turnovers in ending Denver's pursuit of perfection. Indianapolis extended its lead in the AFC South and still hasn't lost consecutive games since Luck arrived in the NFL last year.
Admittedly, this was no typical night for Manning.
The weekend's marquee matchup was the NFL's most anticipated homecoming since Brett Favre went back to Green Bay - with the dreaded Minnesota Vikings - in 2009.
Indy's former franchise quarterback dealt with questions all week about owner Jim Irsay's most recent comments expressing disappointment with winning just one Super Bowl title during the Manning years, then arrived to find out the roof and window at Lucas Oil Stadium would be open on a chilly night inside the house he helped build.
And when he first ran onto the field, some sections in the lower bowl looked like a checkerboard of Colts blue and Broncos orange. They roared for No. 18 throughout a 90-second video tribute featuring some of his most memorable moments with the Colts, including the record-breaking pass to Marvin Harrison for most TDs by a quarterback-receiver duo, the AFC championship comeback against New England and, of course, the evening when he finally hoisted the Lombardi Trophy after winning the Super Bowl in rainy Miami.
Manning responded to the standing ovation by stopping his warm-up throws, taking off his helmet, waving to the fans and mouthing the words "Thank you."
The large video screen then cut to a fan holding a sign that that read "Thanks Peyton But Tonight I'm A Colts Fan."
Afterward, he acknowledged it was an emotional game.
But the Broncos were dealing with far bigger issues on the field.
After Holliday fumbled, Luck hooked up with Darrius Heyward-Bey on the next play to give Indy a 10-7 lead.
After the free kick following the safety Luck found Stanley Havili for a 20-yard TD pass to make it 19-14. Indy never trailed again.
"That's my job, that's how I help my team," Mathis said. "It felt good."
The Colts extended the lead to 26-14 at halftime and 33-14 in the third quarter when Luck scrambled for a 10-yard TD during a drive on which four flags came out on Denver defenders.
Then Manning rallied the Broncos, throwing a 31-yard TD pass to Demaryius Thomas early in the fourth and handing off to Knowshon Moreno for a 1-yard TD run to make it 36-30 with 8:44 left in the game.
Denver forced a punt, giving Manning another chance as the stadium noise subsided. But on the first play, Erik Walden hit Manning's arm and Pat Angerer picked it off to set up Adam Vinatieri's 42-yard field goal.