INDIANAPOLIS -- It was just Peyton Manning's luck.
On his first trip back to Lucas Oil Stadium, he and his teammates had an off night.
His successor and his old team? They got it right.
Andrew Luck threw three touchdown passes and ran for another score Sunday night, handing the Denver Broncos a 39-33 loss -- their first of the season -- without even needing one of Luck's familiar fourth-quarter comebacks.
"It's not real fun watching him," Luck said of Manning. "But he is something to watch."
Heading into the game, Manning and Denver (6-1) 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.
Then came what was supposed to be Manning's happy homecoming. Nothing went right, and now the Kansas City Chiefs (7-0) are the NFL's lone unbeaten team.
He lost a fumble, threw an interception and was sacked four times -- twice by Robert Mathis, one of the few remaining holdovers from the Manning era.
Broncos kick returner Trindon Holliday fumbled twice, losing one that led to a Colts touchdown.
Denver's defense committed inexplicable penalties throughout the second half, giving the Colts more opportunities than they needed, and the Broncos' last good chance fizzled when Denver running back Ronnie Hillman lost a fumble inside the Colts' 5-yard line with 3:03 left in the game.
With Luck and the Colts repeatedly taking advantage, even Manning couldn't rescue the Broncos.
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 (5-2) extended its lead in the AFC South and still hasn't lost consecutive games since Luck arrived in the NFL last year.
"This is a game we need to learn from. We, I guess, had four turnovers and still somehow had a chance to win that game," Manning said. "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. You can go back to different parts of the game and we got behind, mistakes there, but we still had a chance there at the end.
"We certainly have to improve from this game because we weren't as sharp execution-wise as we'd like to be."
Admittedly, this was no typical night for Manning.
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. The crowd 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 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 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.
Mathis' second-quarter strip sack forced a safety and Luck found Stanley Havili for a 20-yard TD pass after the free kick 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.
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 the pace, leading to Adam Vinatieri's 42-yard field goal.
"Hopefully we'll have a chance to play these guys again because that would mean we made the playoffs," Manning said. "I think if there is a next time it may be a little bit easier just because it was somewhat of an emotional week and it can be a little bit draining, I will say that."
The game could prove costly for both teams. Denver cornerback Champ Bailey left in the second quarter with a left foot injury, the same foot that kept him out of the first five games this season. Indy lost Pro Bowl receiver Reggie Wayne in the fourth quarter with what team officials called a sprained right knee. Wayne is expected to have an MRI on Monday. ... Colts cornerback Vontae Davis mistakenly referred to Manning as Tom Brady during a postgame interview on NBC. ... Denver rushed 20 times for 64 yards.
High-ranking Washington Redskins front-office officials and coaches want to part ways with quarterback Robert Griffin III, but are meeting resistance from team ownership, according to sources.
The Packers believe Randall Cobb has a good chance to be ready for the regular-season opener, a source said Sunday after Cobb underwent tests on his injured right shoulder.
Seahawks defensive lineman Frank Clark angered multiple offensive linemen on the Chargers, who accused the rookie of trying to attack San Diego quarterback Philip Rivers while under a pile.
The Chicago Bears will release two-time Pro Bowl cornerback Tim Jennings, a league source told ESPN NFL Insider Adam Schefter.
Colts coach Chuck Pagano said the team should know more about defensive tackle Art Jones' status on Monday.
Jets rookie defensive end Leonard Williams, who gave the franchise a scare with a knee injury Saturday night against the New York Giants, didn't suffer any ligament damage, an MRI revealed.