Jacksonville owned the fourth quarter, flipping momentum for good with Tyson Campbell's interception of Richardson to set up Travis Etienne's 26-yard touchdown run, completing a swing from a 21-17 deficit to a 31-21 lead thanks to 14 points in a span of one minute, six seconds.
Trevor Lawrence passed for 241 yards and two touchdowns and Etienne had 77 rushing yards and five receptions for 27 yards. Jaguars defensive end Josh Allen had a career-best three sacks.
With 5:14 left in the game, Jaguars running back Tank Bigsby plowed 1 yard for a TD and Jacksonville reclaimed the lead 24-21. Jacksonville capped the 11-play drive with three consecutive rushing attempts.
Richardson was sacked four times. He had 40 rushing yards and a touchdown along with a TD pass. He completed 24 of 37 passes for 223 yards.
Colts defensive tackle DeForest Buckner gave the Colts a 21-17 lead in the third quarter with a bizarre sack, forced fumble, fumble recovery and touchdown with 2:41 on the clock. Buckner hit Lawrence as he released a pass from the pocket inside his own 30-yard line. The ball bounced to Bigsby, but he dropped the ball on a hit by Zaire Franklin. Players reacted as if the pass was incomplete, but Buckner scooped it up and stomped down the left sideline for the score.
Richardson's first NFL TD pass was a short throw behind the line to Michael Pittman Jr., who caught the ball on a bubble screen at the "40" painted on the turf and raced to the end zone to tie the game at 14 with 11:25 left in the third.
Lawrence threw a pair of TDs to stake the Jaguars to a 14-7 halftime lead, including a dime down the right side to a diving Zay Jones for an 18-yarder in the second quarter. The first score of the game was Lawrence to Calvin Ridley, which Richardson answered with a 2-yard run on a designed draw behind a convoy of blockers on the first play of the second quarter.
Jones made a highlight reel grab seven yards deep in the end zone, nudging for position while laying out for a well-placed toss from Lawrence.
Playing in his first game in 686 days and regular-season debut with Jacksonville, Ridley caught seven passes for 92 yards in the first half and finished with eight catches for 101 yards and a touchdown.
Without injured starter Jonathan Taylor for the first four games and top backup Zack Moss (inactive, forearm), Indianapolis employed a committee RB approach with poor results, including two lost fumbles from Deon Jackson, who had 13 carries for 14 yards.
Colts rookie running back Evan Hull left the game with a knee injury in the third quarter.
Richardson received medical attention but was able to walk to the sideline under his own power with 59 seconds left in the game trying to run for a touchdown and was replaced by Gardner Minshew.
—Field Level Media