INDIANAPOLIS — Andrew Luck and the Colts ruined Peyton Manning’s return to Indianapolis and handed the Denver Broncos their first loss of the season.
Luck, who replaced Manning as quarterback of the Colts, threw for 228 yards and three touchdowns, ran for another score, and didn’t even need a fourth-quarter comeback to end Denver’s 17-game regular-season streak with a 39-33 victory Sunday night.
While Luck was terrific in prime time, completing 21 of 38 passes, his predecessor was not himself. Manning finished 29 of 49 for 386 yards with three TDs and one interception, and was sacked four times, leaving the Kansas City Chiefs as the NFL’s only unbeaten team.
Manning’s passes sailed high and fluttered, and the man who usually escapes trouble with his quick thinking and quick release was sacked twice and lost a fumble near the goal line. Robert Mathis, one of the few holdovers from the Manning era, got one of his trademark strip sacks in the second quarter — a mistake that led to 9 points for Indianapolis (5-2).
‘‘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 certainly would have liked to have seen it go to a 2-point game down at the end, but we never got there. We certainly have to improve because we weren’t as sharp execution-wise as we would like to be.’’
The offense that was on a record scoring pace and seemed virtually unstoppable over the first six weeks managed only two first-half touchdowns and opened the third quarter with three straight three-and-outs.
Kick returner Trindon Holliday twice fumbled the ball, with one leading to an Indianapolis touchdown, and the defense of the Broncos (6-1) that spent nearly three-fourths of the season playing with the lead came unglued in the third quarter with penalty after penalty aiding Colts drives.
It was not the evening Manning had planned after making the long journey back to Lucas Oil Stadium, the retractable-roof house he helped build by turning the Colts from an afterthought into a perennial powerhouse.
But then this was no typical game.
The weekend’s marquee matchup was the NFL’s most anticipated homecoming since Brett Favre went back to Green Bay — with the rival Minnesota Vikings — in 2009.
Manning had hoped to join Favre as the only quarterbacks to beat all 32 NFL teams and he received a warm welcome.
When Manning 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.
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.’’
‘‘I hope we get a chance to play these guys [again] and maybe if there is a next time, it might be a little easier because it certainly was an emotionally draining week, there’s no doubt about that,’’ Manning said.
Indianapolis took advantage of Holliday’s fumbled punt return, Mathis’s sack that resulted in a safety, and a 20-yard TD pass from Luck to Stanley Havili on the ensuing drive to take a 26-14 lead.
Luck padded the lead with a 10-yard scramble in the third quarter to make 33-14.
After the teams traded field goals, Manning threw a touchdown pass to Demaryius Thomas early in the fourth to make it 36-23 and the Broncos got within 36-30 on Knowshon Moreno’s 1-yard TD run after the Colts lost a fumble.
But Manning’s lone interception with 6:59 to go set up Adam Vinatieri with the game-sealing field goal.
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.