Leftwich will start next week's playoff game at two-time defending champion New England, replacing David Garrard after a six-week layoff because of a broken left ankle.
Even without their offensive leader, the Jags avoided another slow start and gained some much-needed momentum for the playoffs.
Jacksonville scored 27 points in the first half behind Garrard and routed the Tennessee Titans 40-13 Sunday for their eighth win in the last nine games.
Although all eight victories came against teams with losing records, this one felt much different than others in recent weeks.
Jacksonville (12-4), which trailed in the second half in each of the last four games, scored touchdowns on its first two possessions, took advantage of two turnovers and essentially sealed the victory on Derrick Wimbush's 6-yard TD run with 4:11 remaining in the second quarter.
"Two different things happened: We came out and executed real well from the start and they basically gave up and started looking ahead," tight end Kyle Brady said.
The Jaguars already had clinched the No. 5 seed in the AFC playoffs and learned early in the game they will play the Patriots (10-6) on Saturday night.
"We're going against the defending champs," safety Deon Grant said. "You can't ask for anything more than that. We can go up there and shut a lot of people's mouth. If we go up there and be focused and play our game, we'll come out and take care of them boys."
With nothing riding on Sunday's outcome, Jags coach Jack Del Rio rested several starters, including Leftwich and running back Fred Taylor.
Leftwich was the team's No. 3 quarterback against the Titans (4-12), leaving Garrard to start a fifth straight game.
Leftwich broke his ankle Nov. 27 at Arizona. He didn't require surgery, but spent the next few weeks on crutches and in a protective boot. He returned to practice Wednesday and hoped to play against the Titans so he could get ready for the postseason.
Instead, he watched Garrard direct the fast start and Quinn Gray handle mop-up duty.
Garrard was 10-of-16 for 128 yards. Gray replaced Garrard to start the second half and threw his first career touchdown pass, a 10-yarder to rookie Matt Jones that made it 34-0 in the third period. Gray also had a 14-yarder to Ernest Wilford.
The Titans looked eager to finish their second straight losing season, capping it with a three-game losing streak. They avoided their worst loss since 1989 when Bo Scaife caught Billy Volek's tipped pass for a 10-yard touchdown with 55 seconds to play.
"It should eat at everybody," defensive end Kyle Vanden Bosch said. "I don't ever want to be part of a game like this again. We have a lot of problems and a lot of holes to fix."
The Titans also committed a franchise-record 18 penalties for 140 yards, and rookie cornerback Adam "Pacman" Jones was benched by coach Jeff Fisher after he argued with an official during a timeout.
"There's no way we're supposed to lose 40-7 when we played them close last time," linebacker Keith Bulluck said. "I'm not here to point fingers at nobody. You've got to ask those guys if they gave up, and if they tell you they gave up, then they gave up. I didn't see anyone give up."
Matt Mauck started in place of Steve McNair, who sat out with a strained right pectoral muscle. Running back Chris Brown also missed the game with a sprained ankle. Mauck played the first half before giving way to Volek.
The Jaguars led 14-0 after two possessions and made it 20-0 after Mauck threw an interception and later fumbled.
Now, the Jaguars feel like they have something to prove in the postseason.
"It's a great opportunity," Brady said. "Obviously, there's going to be some adversity up there as far as playing at their stadium against the reigning world champions and all the other things that will be spoken about all week long. It's a great opportunity for us to show what kind of team we think we are."
- Jags RB LaBrandon Toefield ran for a career-high 102 yards and had a touchdown.
- WR Jimmy Smith caught four passes for 52 yards on the first three drives and secured his ninth 1,000 yard season in the last 10 years.
- Jags LB Mike Peterson (wrist) and CB Kenny Wright (knee) left the game and did not return.