The Colts entered the weekend having lost every road matchup to the Jaguars since 2014.
Indianapolis gave it a valiant effort, but Jacksonville kept that particular streak alive with a 37-34 victory.
The Jaguars had a 34-20 lead when Tank Bigsby took a carry 65 yards to the end zone with 5:09 left in the fourth quarter. But led by backup Joe Flacco, the Colts were not done yet.
Flacco connected with Alec Pierce for a 46-yard pass down to the 1-yard line on the ensuing drive. Trey Sermon went into the end zone on the next play to make the score 34-27, as the Colts did not go for two even though they were down eight.
A quick Jaguars three-and-out gave the Colts the ball back at their own 23. After a run by Sermon, Flacco again hit Pierce, this time for a 65-yard touchdown to tie the score at 34-34.
But as was the case for much of the day, Indianapolis could not get a stop when it needed one most. Quarterback Trevor Lawrence moved Jacksonville into opponent territory with an 11-yard pass to tight end Luke Farrell. Then a 14-yard pass to Christian Kirk put the Jaguars in field goal range.
Rookie Cam Little hit his 49-yard field goal to give the Jaguars a three-point advantage with 17 seconds left.
Taavon Walker, who strip-sacked Flacco earlier in the contest, closed the game with a sack to win it.
Walker ended the game with five total tackles, including three for loss, with 3.0 sacks, a pass defensed, and a forced fumble.
Lawrence set a new career high with 371 passing yards, eclipsing his previous high-water mark of 368. He completed 28-of-34 passes with two touchdowns and an interception.
Rookie Brian Thomas Jr. had five catches for 122 yards, including an 85-yard touchdown in the second quarter.
On the other side, Flacco finished 34-of-44 with 359 yards with three touchdowns, no picks, and a lost fumble. The Colts were playing without starting quarterback Anthony Richardson, running back Jonathan Taylor, and center Ryan Kelly due to injury.
Right guard Will Fries also had to leave the game due to a right leg injury. He was carted off the field in an air cast.
Now at 1-4, the Jaguars will be across the pond to play the Bears in London next week.
The 2-3 Colts will play another AFC South opponent on the road in the Titans.
