The Colts turned to retired quarterback Kerry Collins and then to Curtis Painter, neither of whom could fill Manning's void.

For the first time since the 1998 season, Peyton Manning was not under the helm at quarterback and it was recently acquired Kerry Collins that would take his position.

However, a three and out from the offense quickly gave the Texans the ball to drive down and score a field goal and take a 3–0 lead.

Collins and the Colts offense was out of sync for much of the first quarter, fumbling two snaps and giving Houston the great field position inside of the Indianapolis 40-yard line.

The first quarter saw both teams getting into offensive and defensive rhythms and ended with the Colts holding only a 3–0 lead on an Adam Vinatieri field goal.

Heading to the second quarter, the Colts offense began to pick up behind Kerry Collins, rookie Delone Carter, and Joseph Addai.

With Cleveland holding a 27–12 lead, Indianapolis was able to score their first touchdown of the game, allowing them to try an onside kick to preserve any chance of a comeback, which they were not able to convert.

Hoping to rebound from their loss to the Cleveland Browns, the Indianapolis Colts remained at home for a week three intra-conference matchup with the Pittsburgh Steelers on Sunday night.

Indianapolis trailed early in the first quarter as Steelers kicker Shaun Suisham got a 48-yard field goal, followed by quarterback Ben Roethlisberger completing an 81-yard touchdown pass to wide receiver Mike Wallace.

The Colts would answer in the second quarter with a 21-yard field goal from kicker Adam Vinatieri, followed by defensive end Jamaal Anderson returning a fumble, forced by Dwight Freeney, 47 yards for a touchdown.

Another defensive turnover allowed the Colts and Vinatieri to score a 25-yard field goal, giving them a 13–10 lead at halftime.

Hoping to rebound from their home loss to the Steelers, the Colts flew to Raymond James Stadium for a Week 4 Monday night duel with the Tampa Bay Buccaneers.

Tampa Bay would tie the game in the third quarter with kicker Connor Barth getting a 46-yard field goal, yet Indianapolis came right back with Painter hooking up Garçon again on a 59-yard touchdown pass.

Afterwards, the Buccaneers tied the game with Freeman completing a 13-yard touchdown pass to wide receiver Preston Parker.

After dropping their first four games of the season, the Indianapolis Colts came back to Lucas Oil Stadium to take on the Kansas City Chiefs.

Two touchdown passes from Cassel, to Dwayne Bowe and Steve Breaston respectively, gave the Chiefs 21 unanswered points and completed the comeback, winning the game 28–24, dropping the Colts to 0–5 on the season.

With both defenses performing well throughout the remainder of the first half with the only other scores coming on a Donald Brown touchdown run for the Colts, and a Mike Nugent field goal.

A Dallas Clark touchdown reception from Curtis Painter allowed the Colts to cut the game to a 20–17 affair with 9:33 remaining in the fourth quarter.

They would eventually move ahead 31–0 in the 2nd quarter as Jed Collins ran for a 1-yard touchdown followed by John Kasay nailing a 23-yard field goal.

In the 2nd half, the Saints score 4 consecutive touchdowns with Brees hooking up with Jimmy Graham on a 4-yard and 2-yard to increase their lead to 41–7 and then 48–7 in the 3rd quarter.

The Colts’ loss was the most lopsided game of the 2011 NFL season and the first time a team had allowed 60 or more points since January 2000, when the Jacksonville Jaguars humiliated the Miami Dolphins 62–7 in the divisional round playoffs.

The Titans would score 20 unanswered points in the first half alone as Rob Bironas would kick a 51-yard field goal for a 3–0 lead in the first quarter, and in the 2nd quarter, Jason McCourty would recover a blocked punt in the end zone sending the game to 10–0, followed up by Bironas nailing a 50-yard field goal for 13–0 and eventual halftime lead of 20–0 when Nate Washington ran for a 3-yard touchdown.

The Colts finally got on the board as Jerraud Powers returned an interception 6-yards for a touchdown making the halftime lead 21–7.

Though the Colts managed to move within 5 points as Curtis Painter found Reggie Wayne on a 56-yard pass (with a failed 2-point conversion) for a 24–19 game.

Despite putting up 21 points in the fourth quarter with Dan Orlovsky under center, the Colts again lost on the road to the New England Patriots.

With the loss, the Colts fell to 0–12 and became the ninth team in NFL history to start 0–12,[12] and the third franchise after the Lions and Buccaneers to suffer this ignominy twice.

With this loss, the Colts fell to 0–13 and became the sixth team in NFL history to start a season at 0–13,[12] and the first franchise to suffer this ignominy on multiple occasions.

After starting 0–13 and looking most likely to become the second team in NFL history to go 0–16 after the 2008 Detroit Lions, the Colts finally won a game.