That was September 2010, and a lot has changed since then.
Now, Manning has led his new team to a 6-0 record, and a visit to Lucas Oil Stadium to play his former team on Sunday night looms.
However, this game will be about more than just a homecoming for Manning, though you likely won't hear anything else up until kickoff.
It is a very important contest for two of the AFC's top teams. Here, we've chosen five matchups that will help determine the outcome of this one.
The Broncos lead the all-time series 11-10, but they haven't beaten Indianapolis since January 2005.
The Denver Broncos have a seemingly never-ending supply of offensive weapons, but the one opposing defenses have not had any kind of answer for is Julius Thomas.
The big tight end has caught 31 passes on the year already and more impressively, he's found the end zone seven times.
It remains to be seen if the Colts will have safety LaRon Landry for this game as he has been dealing with an injured ankle. If not, slowing down Thomas will be even more of a chore.
Thomas could easily find holes in the middle of the field, making him a prime target for Peyton Manning.
Though Denver has managed to win all of their games, the pass defense has taken a beating in recent weeks.
It was one thing for Tony Romo to throw for over 500 yards on them, but they gave up plenty through the air to Chad Henne and the winless Jaguars last Sunday.
That Week 6 game marked the season debut for Champ Bailey, who was finally able to go after dealing with an injured foot suffered in the preseason.
But Bailey wasn't much help. The only play he made was on a two-point conversion attempt by Jacksonville.
Bailey could do nothing about Justin Blackmon, who had a career day against Denver, catching 14 passes for 190 yards.
Reggie Wayne, who on Monday night became just the eighth wide receiver to catch 1,000 career passes, could have the same type of day.
Wayne is a great route-runner who could exploit the Broncos secondary all night long on slants and crossing routes over the middle.
If the Broncos have an area to work on, it is their pass defense. Colts quarterback Andrew Luck will take everything the Broncos give him. It will be Bailey's job to limit those opportunities.
Following the Colts' acquisition of running back Trent Richardson, it seemed the team had found the piece that could make their offense go from good to great.
That hasn't worked out so far. As a member of the Colts, Richardson has run for just 191 yards in four games.
Still, a popular game plan against the Broncos is to keep Peyton Manning off the field. Nothing will achieve that better than a sound running game.
The Colts know this firsthand, as they watched the San Diego Chargers do it to them Monday night.
The Broncos will come into the game ranked No. 1 in rushing defense in the league, giving up just 69.8 yards per game.
That bodes well for Denver, but it doesn't mean the Colts will be intimidated and won't try to establish Richardson as a force in the game.
Thrust into a starting role following a season-ending injury to left tackle Ryan Clady, Chris Clark has filled in admirably.
But the challenge of protecting Peyton Manning's blind side never seems to get easier.
On Sunday night, Clark will have to deal with Robert Mathis, who is currently tied for the NFL lead in sacks this season with 9.5.
As good as Mathis has been, he was rendered nearly useless in the Colts' loss to San Diego on Monday night.
San Diego left tackle King Dunlap did his job to keep him away, and Mathis never really sniffed a sack in that game.
Clark needs to study that game tape because that is the only contest this season in which Mathis didn't register at least one sack.
The Broncos have played the first six games on their schedule, winning them all. With those games behind them, they now have the added bonus of getting Von Miller back.
Miller, easily one of the league's premiere pass-rushers, has served his league-mandated six-game suspension for failing the substance abuse policy, and he will likely be ready to wreak havoc in his return.
Miller identified his first goal as wanting to regain the trust of his teammates, according to Jeff Legwold of ESPN. Nothing will do that faster than showing them he can still be the player he has been over the course of his first two years.
Miller has tallied 30 sacks in his first two years in the league, and the Colts will have to employ a completely different approach on offense than they would if he weren't playing.
So how will Indianapolis choose to block him and how many players will it take? If Miller faces constant double teams, it will free up another Denver defender, like Derek Wolfe, to get to the quarterback.
In their loss to the Chargers on Monday night, Andrew Luck faced a lot of pressure. Though he was only sacked once, he was forced into several bad throws.
If Denver is able to apply the same kind of pressure, the Colts are in for a long night.