The Colts' rival, the New England Patriots, lost to the Denver Broncos in the Divisional round of the playoffs.

However, the Colts lost their first playoff game in heartbreaking fashion to the eventual Super Bowl champion Steelers, when placekicker Mike Vanderjagt missed a crucial field goal.

The 2005 Colts set an NFL record by winning twelve games in which they never trailed at any point in the contest and still stands as of 2023.

[1][note 1] The 2005 Colts were the first team to start the season with 13 straight wins and lose an opening playoff game, although this would be repeated by the 2011 Green Bay Packers.

The Colts had a busy offseason with the main focus to sign star running back Edgerrin James to a new contract.

Baltimore kicker Matt Stover missed three field goals, and gave the Colts more opportunities to score.

Also of note, after Cato June's interception return, kicker Mike Vanderjagt scored his 900th point in the NFL.

The Rams jumped out to a 17–0 lead on the Colts in the RCA Dome in front of a Monday Night Football audience, and few could believe it.

After two interceptions by MLB Cato June that set up two touchdowns, an interception and a fumble recovery by CB Nick Harper that also set up two touchdown scores, the Colts scored all 45 of their points in three quarters and held the Rams to just 11 points in those quarters.

However, that did not hold up in the second half as the Colts scored 24 second-half points and held Houston to −4 total yards on offense.

The opposing quarterback, Carson Palmer also had marvelous stats, as he finished with 25 pass completions on 38 attempts, two touchdowns, and one interception.

[2] Colts WR Marvin Harrison also reached 900 receptions for his career in this game, and he is the fastest player to do so in NFL history.

After the Steelers went three-and-out on their first possession of the game, the Colts scored on the first play of their first drive when quarterback Peyton Manning threw an 80-yard touchdown strike to WR Marvin Harrison.

The Colts were the fifth team in NFL history to start a season 12–0, and also clinched a playoff spot with this win against the Titans.

But the Colts had to wait one more week to clinch the AFC South Championship and a first-round bye in the playoffs.

Jaguars QB David Garrard (who was starting in the place of Byron Leftwich) was 26 of 35 for 250 passing yards, and had one touchdown.

After the Colts defeated the Jaguars, they became only the fourth team in NFL history to start a season 13–0, after the 1934 Chicago Bears, the 1972 Miami Dolphins, and the 1998 Denver Broncos.

However, Dungy's decision did not come from the sidelines, because two days earlier, his eldest son, James, had committed suicide in his apartment.

The game featured the highest scoring and winningest teams against each other, and each looking to set a franchise record for most wins in a season.

In addition, the schedule makers set a record with the first regular season game where the teams combined for at least 25 victories.

The Colts faced the Arizona Cardinals at the RCA Dome, and in front of an emotional and proud crowd.

A deputy from the Hillsborough County Sheriff's Department performed CPR on the 18-year-old Dungy before an ambulance transported him to University Community Hospital, where James was pronounced dead.

The Operations Manager at the Hillsborough County Medical Examiners Department said that the cause of death was an apparent suicide.

On February 17, 2006, after the autopsy was performed, Dr. Jacqueline Lee of the Hillsborough County Medical Examiner's Office stated that Dungy had hanged himself from a bedroom ceiling fan with a leather belt.

Two months before his death, James Dungy had also been treated for a prescription drug overdose on October 21, 2005. at RCA Dome • Indianapolis, Indiana

The Colts rallied in the final quarter to cut the deficit 21–18, with quarterback Manning's 50-yard touchdown pass to tight end Dallas Clark and running back Edgerrin James’s 3-yard touchdown run (and Reggie Wayne’s successful two-point conversion reception).

James' touchdown came a few plays after an interception by Pittsburgh safety Troy Polamalu was overturned by instant replay (a reversal that the league would later admit was a mistake [2]).

But with 1:20 left in the game, Manning was sacked on fourth and 16 at the Colts' 2-yard line, and the ball was turned over to the Steelers on downs.

However, the Steelers were forced to advance the ball towards another score instead of taking a quarterback kneel because the Colts still had three timeouts remaining.

Eventually, the Colts then advanced to the Pittsburgh 28-yard line, but kicker Mike Vanderjagt, who had been perfect at home in the playoffs, missed a 46-yard game-tying field goal attempt wide right with 17 seconds remaining, and the Steelers ran out the clock.