The victory completes a remarkable turnaround for the Jags, who lost five straight earlier in the season yet rallied to 4-8, before securing five straight wins to top the division ahead of the Titans (7-10).
Tennessee scored the first 10 points of the game but the Jags hit the lead for the first time with 2:51 remaining in the fourth quarter when Rayshawn Jenkins forced a fumble from Titans QB Joshua Dobbs which Josh Allen scooped up for the go-ahead touchdown.
That TD marked a brilliant second-half performance by the Jags' defense, who had four sacks for the game, allowing only three points after trailing 13-7 at half-time.
Jacksonville clinched their fourth division title and qualified for the playoffs for the first time since the 2017 season, having only won four games in the previous two years.
Jags QB Trevor Lawrence was not at his best but threw 20 of 32 passes for 212 yards, including a touchdown pass to Christian Kirk late in the second quarter. Kirk had 99 yards on six receptions.
The Titans had opened up a 10-0 lead from Dobbs' TD pass to Chigoziem Okonkwo with 5:32 left in the second quarter.
Running back Derrick Henry ran for 109 yards on 30 carries for the Titans, who missed the playoffs after seven straight losses.