Mahomes threw touchdown passes to Skyy Moore and Travis Kelce as the Chiefs (1-1) rebounded from a season-opening 21-20 loss to the Detroit Lions. Mahomes completed 29 of 41 passes with one interception and Kelce caught four passes for 26 yards after missing the opener due to a hyperextended knee.
Kansas City's Chris Jones and George Karlaftis each recorded 1.5 sacks. It was Jones' first game since ending his holdout.
The Chiefs had a 399-271 yardage edge while defeating Jacksonville for the eighth straight time, including last season's 27-20 in the AFC divisional round of the playoffs.
Trevor Lawrence completed 22 of 41 passes for 216 yards for the Jaguars (1-1). Christian Kirk grabbed 11 passes for 110 yards, but fellow wideouts Zay Jones and Calvin Ridley each failed to get both feet down on end-zone throws on two occasions apiece.
The Chiefs were sluggish on offense in the first half but opened the third quarter with a seven-play, 81-yard touchdown drive.
Isiah Pacheco began the drive with a 31-yard run and Mahomes converted two third-down throws, including a 9-yard scoring pass to Kelce to make it 14-6 with 11:30 remaining in the third quarter.
The score marked the 47th time Mahomes connected with Kelce on a touchdown pass. That set a new Kansas City record, surpassing the 46 times Len Dawson hooked up with Otis Taylor from 1965-74.
The Jaguars had a stellar opportunity early in the fourth quarter when they had first-and-goal from the Chiefs' 1-yard line, but they had to settle for Brandon McManus's 22-yard field goal. Lawrence lost 3 yards on a run, Zay Jones got just one foot down in the end zone on a second-down pass and Calvin Ridley got no feet in on a third-down throw.
Not cashing in was costly as the Chiefs answered with a 13-play, 55-yard drive. Harrison Butker capped it with a 38-yard field goal to make it 17-9 with 8:10 remaining.
The Jaguars made another dash. On fourth-and-12 from the Kansas City 16, Lawrence threw to Ridley in the back of the end zone. Ridley bobbled the ball before corralling it but only had one foot down on the incompletion with 4:18 remaining.
Mahomes and Moore teamed up on a 54-yard pass play with 1:50 left to seal it for the Chiefs, who ran out the clock.
Kansas City led 7-6 at halftime. Mahomes threw a touchdown to Moore, while McManus kicked field goals of 32 and 49 yards for the Jaguars. Jones also had just one foot down in the end zone on a would-be catch early in the second quarter before McManus' first field goal.
—Field Level Media