The touchdown pass capped off a stellar night for Roethlisberger, who completed 26 of 41 passes for 309 yards, three touchdowns and one interception.
Steelers' perennial nemesis Rashean Mathis struck again on Pittsburgh's opening possession, intercepting Roethlisberger and returning it 72 yards for a touchdown to give Jacksonville a 7-0 lead.
The pass was intended for Santonio Holmes, who slipped coming out of his cut and never saw the ball.
The Steelers, however, answered immediately, putting together a 71-yard scoring drive capped off by a 1-yard pass from Roethlisberger to tight end Heath Miller. It was Miller's first TD catch of the season.
But Jacksonville reclaimed the lead moments later when Steelers' cornerback Ike Taylor was penalized 40 yards for a pass interference penalty in the end zone and Maurice-Jones Drew made Pittsburgh pay with a 1-yard touchdown run that gave the Jaguars a 14-7 advantage.
The Steelers went to their no-huddle offense on their next possession and it led to a 38-yard Jeff Reed field goal that trimmed the Jacksonville lead to 14-10 early in the second quarter.
Pittsburgh took a 17-14 lead on its next possession when Roethlisberger connected with Nate Washington on a 48-yard bomb and increased it to 20-14 with a 23-yard Reed field goal just before halftime.
Jacksonville regained the lead early in the fourth quarter when David Garrard tossed a 24-yard touchdown pass to tight end Mercedes Lewis to give the Jaguars a 21-20 advantage.
But Roethlisberger drove the Steelers 80 yards in the game's final five minutes for the go-ahead score and the Steelers defense forced the Jaguars to turn the ball over on down with 25 seconds left to seal the win.