While both teams competed for the AFC South during the late 2000s, the Colts largely controlled the rivalry, thanks to great quarterback play from Peyton Manning and Andrew Luck.

The rivalry is characterized by the Jaguars ability to secure significant upsets against the dominant Colts, even though they do not consistently field competitive teams.

[7][8][9] Since the inception of the AFC South division in the 2002 season, the Jaguars have recorded more wins against the Colts than their counterparts, the Tennessee Titans and the Houston Texans.

[16] Although the team experienced championship success,[17] owner Robert Irsay threatened to move the franchise due to issues with their home venue, the Baltimore Memorial Stadium.

[23] Although they faced challenges and were not the frontrunners compared to other cities, the NFL ultimately voted to award Jacksonville an expansion team on November 30, 1993.

During the 1996 season playoffs, the Colts were defeated by the Pittsburgh Steelers, whereas the Jaguars unexpectedly advanced to the AFC Championship by overcoming the Buffalo Bills and the Denver Broncos, only to fall to the New England Patriots.

[33] Initially, the NFL offered Wayne Huizenga, owner of the Dolphins, the opportunity to move to the more geographically suitable AFC South over the Colts, potentially fostering an in-state rivalry with the Jaguars.

Although the Colts had lost the inaugural AFC South title to the Titans the week prior, they still have the opportunity to secure a playoff berth with a victory against the eliminated Jaguars.

In the closing moments, the Colts' defense held firm, securing a 20–13 victory over the Jaguars, completing a sweep in their initial matchups as divisional rivals and earning a wild card spot in the playoffs.

[39] A standout moment from the game occurred when Colts' rookie DB Mike Doss caused Jaguars' RB Fred Taylor to fumble the ball.

However, Fred Taylor fulfilled his promise with a 32–yard run, evading Mike Doss as he fell, and reached the end zone, putting the Jaguars ahead with just one minute left in the game.

[15] The Colts embarked on a winning streak that ultimately secured them the AFC South title,[44] and were locked in the 3rd seed after a 34–31 overtime victory over the San Diego Chargers as they entered the final week.

[51] In the playoffs, the Jaguars were eliminated by the Patriots,[52] whereas the Colts experienced a surprising defeat in a notable game against the eventual Super Bowl champions Steelers.

The Jaguars were eliminated from contention due to subpar performance and injuries,[70] while the Colts saw their consecutive AFC South title streak come to an end at the hands of the Titans.

Trailing by 10 points as they entered the fourth quarter, Manning led a comeback for the Colts, and a pick-six allowed them to take the lead, winning 31–24 and clinching the 5th seed in the playoffs.

Ultimately, the decisive moment came when Manning connected with WR Reggie Wayne for a 65–yard touchdown pass, allowing the Colts to secure a 35–31 victory.

[87] The game marked a turning point for the Colts, who subsequently enhanced their performance for the remainder of the season,[88] ultimately securing the 5th seed[89] and avenging their earlier loss to the Jaguars.

[96] Andrew Luck was unable to participate in his first NFL game due to a right shoulder injury in the 2015 season, as the Colts faced the Jaguars on October 4 in Indianapolis.

In response, Colts backup QB Matt Hasselbeck orchestrated a 53–yard drive that ended with K Adam Vinatieri successfully converting a game-winning 27-yard field goal, winning 16–13.

This victory marked a franchise record for the Jaguars in terms of points scored in a regular season game, represented their largest victory over the Colts with a 35–point differential, ended a six-game losing streak against them, and snapped the Colts' 16-game winning streak in the AFC South, which stands as an NFL record in all divisional play.

[100] In a crowd that evenly supported both teams, the Colts struggled with dropped passes and penalties, allowing the Jaguars to establish a 23–6 lead by the beginning of the fourth quarter.

[103] The Jaguars, initially expected to be one of the weakest teams,[104] have surprisingly started strong, thanks in large part to their defense, which was being nicknamed "Sacksonville".

[105] When the Jaguars faced the Colts on October 22 in Indianapolis, their defense dominated, sacking backup QB Jacoby Brissett 10 times, equaling the franchise's single-game record set in their season-opener against the Texans, and securing a 27–0 shutout victory.

The Jaguars attempted a rally and were approaching Indianapolis territory to tie the game, but a fumble by WR Rashad Greene ultimately secured a 29–26 victory for the Colts.

The Colts, who entered the game ranked fourth in the league for scoring, passed on two field-goal attempts in the first half, including one initially successful but later nullified.

[9] In the game, the Colts didn't punt once, allowed no sacks of QB Philip Rivers, outgained the Jaguars 445–241 in total yardage and won the time-of-possession battle 33:23 to 26:37.

Although they had lost the AFC South title to the Titans the week prior,[130] a victory against the struggling 2–14 Jaguars, who were on an eight-game losing streak, would clinch a playoff berth for the Colts.

[134] The Jaguars' defense, which had allowed 50 points to the Patriots the week prior,[135] limited Jonathan Taylor, the NFL's leading rusher, to 77 yards on 15 carries and stopped him on fourth down twice.

[139] The Colts managed to secure a measure of revenge when QB Matt Ryan delivered a game-winning 32–yard touchdown pass with just 17 seconds remaining on October 16 in Indianapolis, leading the team to a 34–27 victory.

[145] In their second encounter on October 15 in Jacksonville, Richardson did not take the field as the starter; instead, former Jaguars quarterback Gardner Minshew led the Colts.