The Broncos were clinging to a 21-19 lead midway through the third quarter before Peyton Manning led them on a pair of touchdown drives, each capped by a Moreno TD run.
Moreno amassed 104 yards of total offense on 15 carries and seven receptions. Manning completed 28-of-42 passes for 295 yards with two scoring strikes as Denver (6-0) ran off a 17th straight regular-season victory.
Wes Welker contributed six catches for 63 yards and a touchdown for the Broncos.
Paul Posluszny kept the winless Jaguars (0-6) in the game with a 59-yard interception return for a touchdown late in the first half.
Justin Blackmon compiled 190 yards on a career-high 14 catches in his second game back from a league suspension and backup Chad Henne completed 27-of-42 passes for 303 yards for Jacksonville.
Henne, subbing for the injured Blaine Gabbert (hamstring), was picked off twice in the fourth quarter.