Manning's last game as a Colt was on January 8, 2011, a 17–16 loss to the New York Jets in the Wild Card Round and would sign with the Denver Broncos a year later, on March 20, 2012.

The Colts eventually got the offense going late in the second quarter by scoring on a touchdown reception by Reggie Wayne, which broke the lead down to one possession.

The 2010 meeting between the Indianapolis Colts and the New York Giants marked the second time that the two quarterback brothers of Peyton and Eli Manning met in a football game, the last coming in 2006.

After switching possession, the Colts were able to respond with a touchdown drive that included Blair White, who was just signed from the practice squad prior to the game.

The defense was able to stop the Broncos on their next possession allowing the Colts to win 27–13, and take their second straight game of the season, improving their record to 2–1.

With the first possession of the ballgame, the Colts drove down the field with a mix of pass and run plays, scoring the opening touchdown of the game.

In the second quarter Maurice Jones-Drew scored on a touchdown run giving the Jaguars their first lead of the day, with the Colts eventually responded and tying the up 14–14 going into halftime.

With the Colts trailing midway through the fourth quarter, Peyton Manning drove the team down the field to score on a Joseph Addai run.

After losing the previous week to Jacksonville, the Indianapolis Colts came back home to Lucas Oil Stadium to battle with an undefeated Kansas City Chiefs team.

The Chiefs' head coach, Todd Haley opened up the ballgame with an onside kick intended to give Kansas City the ball first.

Coming off their home win over the Chiefs, the Colts flew to FedExField for a Week 6 interconference duel with the Washington Redskins on Sunday night.

In the second quarter, the Colts regained the lead as Manning hooked up with wide receiver Austin Collie on a 5-yard touchdown pass, followed by kicker Adam Vinatieri booting a 43-yard field goal.

Washington tried to rally as quarterback Donovan McNabb completed an 8-yard touchdown pass to running back Keiland Williams, yet Indianapolis' defense held tough to preserve the victory.

With about nine and a half minutes left in the second quarter, Peyton Manning suffered a painful hit from two Redskins defenders in which his back and neck bent violently backwards.

Houston came out of the locker room improved, however Peyton Manning and the Indianapolis offense continued to be productive scoring a touchdown on a Reggie Wayne reception in the beginning of the first half.

A hard hit on wide receiver Austin Collie, who was returning from injury that week, caused a 10‑minute delay in the game in which he was strapped to a stripper and taken to a nearby hospital, where he was diagnosed with a concussion.

Following their third loss of the season, the Indianapolis Colts entered their home game against the Cincinnati Bengals with a chance to regain the lead in the AFC South.

However, as the quarter wore on the defense began to allow larger gains and the Bengals were able to score a touchdown and a field goal in the last ten minutes of the half.

They tried to cut the lead as Manning made a 6-yard TD pass to WR Blair White, but the Chargers controlled the second half with Kaeding getting a 30-yard field goal, which was shortly followed by FS Eric Weddle returning an interception 41 yards for a touchdown, then with FB Mike Tolbert getting a 3-yard TD run, and Kaeding making a 20-yard field goal, settling both records to 6–5.

In the first quarter the Colts caused problems with their defense after RB Tashard Choice got a 20-yard TD run, followed by kicker David Buehler hitting a 40-yard field goal.

The Cowboys increased their lead after Buehler made a 46-yard field goal, and with LB Sean Lee returning an interception 31 yards for a TD.

The Colts got a slight lead with RB Javarris James getting a 1-yard TD run, followed by WR Taj Smith returning a blocked punt 2 yards for a touchdown.

Trying to snap a three-game losing streak, the Colts flew to LP Field for a Week 14 AFC South duel with the Tennessee Titans on Thursday night.

The Colts would add onto their lead in the second quarter as quarterback Peyton Manning found wide receiver Pierre Garçon on a 1-yard and a 19-yard touchdown pass.

Tennessee began to cut away at their deficit in the third quarter as quarterback Kerry Collins completed a 7-yard touchdown pass to tight end Craig Stevens, yet Indianapolis responded with a 21-yard field goal from kicker Adam Vinatieri.

The Titans tried to rally as Collins completed a 9-yard touchdown pass to tight end Bo Scaife, yet Indianapolis rose to the challenge with Vinatieri booting a 47-yard field goal.

The lead was narrowed with a 22-yard field goal from kicker Josh Scobee, but the Colts scored again as Manning found Collie again on a 27-yard TD pass.

They trailed again after kicker Sebastian Janikowski hit a 59 and a 38-yard field goal, but responded to take the lead back with QB Peyton Manning completing an 18-yard TD pass to TE Jacob Tamme.

The Raiders tried to come back after QB Jason Campbell threw a 6-yard TD pass to TE Zach Miller, but Manning ran for a first down on the Colts ensuing possession to seal the game.

at Lucas Oil Stadium; Indianapolis, Indiana Hoping to clinch a playoff spot the Colts played on home ground for a division rivalry rematch against the Titans.