The Texans walked off Everbank Field with a 45-7 loss as Jaguars fans celebrated their first playoff berth in a decade.
"They're one of the better teams in football," head coach Bill O'Brien said after the game.
That didn't lessen the sting of one of the worst losses in franchise history in a season marred by injury. The Texans had previously won three consecutive games in Jacksonville under O'Brien.
"It was just a slow start offensively, just couldn't convert on third down," O'Brien said. "It just snowballed for the whole team, just wasn't good."
T.J. Yates completed 12-of-31 for 128 yards for one touchdown and one interception. DeAndre Hopkins caught four passes for 80 yards and a touchdown, setting a single-season career high of 12 touchdowns with two games remaining.
However, the Texans were scoreless until the second half. Trailing 31-0 at halftime, Houston punted on six consecutive drives before turning the ball over on the final drive of the first half on an interception.
"Obviously, they are an incredible defense," Yates said. "They did a great job covering, great job rushing the passer, creating some confusion up front. We knew what we were going up against coming into the game and we didn't execute the things we thought would work against them. There were plays out there to be made, we just didn't make them."
"I don't think we could convert on third down on offense," O'Brien said. "That was a big thing. We couldn't stay on the field so we kept putting our defense back out there and that's tough against Jacksonville and they are going to wear you down after a while. We just had trouble converting on third down."
Houston was 4-of-16 on third down, converting just 25 percent. Penalties also proved costly with 14 flags for 127 yards. The Jaguars had 464 net yards of offense against the Texans.
Blake Bortles was 21-of-29 for 326 yards and three touchdown passes. Marcus Gilchrist had a team-high six tackles and one tackle for loss. Jadeveon Clowney recorded four tackles and three quarterback hits. Brian Cushing had the lone sack of the day.
With the loss, the Texan fall to 4-10 on the season and will next face Pittsburgh at home in Week 16.
The Texans faced the Jaguars at EverBank Field in a Week 15 contest.