In his second try, Manning beat his old team and joined Brett Favre as the only quarterbacks to beat each of the current 32 NFL franchises.
"It means I'm old," Manning cracked.
More heart-pounders like this and Manning will go gray.
With Welker serving a four-game suspension for violating the NFL's policy on performance-enhancing drugs, the Broncos couldn't convert third downs, going 1 for 7 in the second half after a first half in which they went 6 of 7.
"We've got to find a way to play all four quarters as an offense," Manning said. "Thank goodness the defense picked us up when the offense wasn't doing their job quite as well."
"We did manage to take advantage of some opportunities in the second half that we didn't in the first. It was good to get that two-minute drive right at the end of the half," said Luck, whose 9-yard scamper made it 24-7 at the break and provided a spark for the Colts.
Both teams left the stadium talking about needing to clean up their play.
"It wasn't the best win, but guess what, it was a great opener," said DeMarcus Ware, who had 1.5 sacks in his Denver debut after a franchise-high 117 in nine seasons in Dallas.
Safety Rahim Moore had two interceptions in his first game since Nov. 17, when he underwent emergency surgery on his left calf because of a rare muscle condition known as compartment syndrome.
"We said we've got to make a play to win the game," Roby said. "We can't rely on the offense. It's on us."
Thomas' trio of touchdown grabs tied a franchise record for most in a game. Hall of Famer Shannon Sharpe did it three times.
"I feel like it's my responsibility to make big plays when my team needs it," Thomas said. "Something I pride myself on is being ready for man coverage. It's like backyard football with your little brother or cousins. I don't believe you should be covered 1-on-1."
Denver's defense came up with two big stops deep in its territory during a third quarter dominated by Indy. On fourth down at the 1, linebacker Brandon Marshall, making his first career start, stuffed Luck's run up the middle.
Last year, Manning let both his emotions and the Colts get the best of him in a 39-33 loss at Lucas Oil Stadium, the house he helped build.
And the five-time MVP didn't have to worry about suspended pass-rusher Robert Mathis, who hounded him last year with two of the season-high four sacks Manning endured.
Manning was sacked once on this night. But he was victimized by more than a half-dozen drops, finishing 22 of 36 for 269 yards with no interceptions.
Notes: Thomas had seven catches for 104 yards but also fumbled a ball that teammate Bubba Caldwell recovered and couldn't corral Indy's successful onside kick in the fourth quarter. ... Colts LB Cam Johnson (triceps) and LB Jerrell Freeman (hamstring) were injured. ... Broncos special teams ace David Bruton injured a shoulder.
Copyright 2014 by The Associated Press