Rookie Josh Allen, the seventh overall pick, will start in Ngakoue's place.
This will be the first game Ngakoue will miss in his three-plus seasons. The only game he has failed to start since the Jaguars drafted him in the third round in 2016 was the season opener his rookie year.
"It's a shame," coach Doug Marrone said. "I spoke to him and he really wants to play. He's like, 'I want to play. I don't really care. I want to get out there.'
"You don't really see that a lot, but that's how he's been."
Ngakoue is already third in franchise history with 29.5 sacks and he also has forced 10 fumbles and has 29 tackles for loss. Texans quarterback Deshaun Watson has been sacked an average of 3.52 times per game in his career. Per ESPN Stats & Information only three players have been sacked more per game in the first two seasons of their careers since sacks became an official stat in 1982: Randall Cunningham, Jake Plummer and Blake Bortles.
In addition, left tackle Cam Robinson (hyperextended right knee) has been cleared to play against the Texans, but Marrone is opting to hold him out as a precaution. Robinson also missed the season opener with the right knee injury. He missed the final 14 games of 2018 with a torn left ACL and only came off the PUP list on Aug. 12.
"Just want to make sure that he gets the work in," Marrone said. "He's missed a lot of training camp."
First-year player Will Richardson will make his second consecutive start in Robinson's place.