The Colts, who have made a stuttering start to the season, on Sunday outfoxed the Broncos to secure a deserved 27-24 victory as Manning’s return to his former stamping ground ended in defeat.
Manning, 39, had entered the game at the Lucas Oil Stadium needing 284 yards to overtake Brett Favre’s record passing total of 71,838.
Yet Manning was left an agonising three yards short of surpassing Favre’s benchmark after throwing for 281 yards and two touchdowns.
Crucially, however, Manning gave up a vital interception late in the fourth quarter to hand possession back to the Colts, who then ran down the clock on the ensuing drive to close out the game under the calm guidance of quarterback Luck.
“Finally, we didn’t shoot ourselves in the foot,” said Luck, who has struggled with turnovers and sacks so far this season.
“The defense and special teams were great complementary pieces. And for once we weren’t down three scores, which limits what you can do offensively.”
Manning said Denver had simply underperformed.
“When you don’t play as well as you would like, it’s hard to win on the road,” Manning said.
“We just didn’t play well enough.”
The Broncos’ defeat leaves the New England Patriots, the Carolina Panthers and the Cincinnati Bengals as the three remaining unbeaten teams this season.
The Patriots and the Panthers extended their perfect starts to the season with contrasting victories over the Washington Redskins and Green Bay Packers.
Tom Brady and the Patriots made it eight wins out of eight with a comfortable 27-10 win over the Redskins in Foxborough while Carolina survived a thrilling late Green Bay comeback to win 37-29 in Charlotte.
Brady threw two touchdown passes while running back LeGarrette Blount ran for 129 yards and a touchdown as the Super Bowl champions took command of the contest early on to leave the Redskins at 3-5 for the year.
Victory came at a cost for the Patriots, however, with left tackle Sebastian Vollmer leaving the game with a head injury and running back Dion Lewis also hobbling out of the match with a knee problem.
A pulsating duel in Charlotte saw Cam Newton and the Panthers defy a late onslaught by Aaron Rodgers and the Packers to move to 8-0.
The Panthers had looked to be cruising to victory after holding a 23-point lead at 37-14 with 9:22 left in the fourth quarter against the Packers, whose offensive threat had been mostly snuffed out by the Carolina defence. But Green Bay were given a glimmer of hope when a 29-yard screen pass to running back James Stark produced a touchdown.
Rodgers then hit tight end Richard Rodgers from three yards for a further touchdown to help take the score to 37-29 with 3:43 left.
The Packers seemed to be closing in on a miraculous comeback when they won a quick turnover and advanced down field on Carolina’s next possession.
But Aaron Rodgers was picked off on fourth and goal as Carolina’s defence held firm and the Panthers held on for the win.
The victory could prove decisive in the eventual playoff picture in the National Football Conference, with Panthers now well placed to deny the rival Packers, who fell to 6-2, homefield advantage.
In other games, a last-gasp 38-35 win for the Pittsburgh Steelers over the Oakland Raiders was overshadowed by a fresh injury to veteran quarterback Ben Roethlisberger.
Roethlisberger, who threw for 335 yards and two touchdowns, limped out of the game in the fourth quarter with an injury to his left foot.
The 33-year-old only returned from injury last week in a loss to the Cincinnati Bengals after missing four games with a left knee problem.