Miller suffered the injury when his knee was hit by the helmet and shoulder pad of Dallas Cowboys defensive tackle Maliek Collins during the first quarter of Saturday's preseason game. Miller's left foot was planted on contact, and the knee buckled inward.
Miller, 28, was seeing his first action of the preseason after rushing for 973 yards and five touchdowns in 14 games last season, reaching the Pro Bowl for the first time. He is entering the final season of a four-year, $26 million contract.
Recent trade acquisition Duke Johnson is expected to see an increased workload for the Texans, who released fellow running back D'Onta Foreman this offseason.
Johnson was acquired from the Cleveland Browns for a conditional draft pick earlier this month, with the selection becoming a third-rounder if the 25-year-old is active for at least 10 games.
"I think it's a package deal," Houston coach Bill O'Brien said when asked how the team will address the workload after losing Miller.
"It's kind of early to talk about that, to nail that down right now, but, obviously, Duke would be in there."
Johnson, Cleveland's third-round pick in 2015, spent four seasons with the Browns. He totaled 3,456 yards from scrimmage along with eight receiving and five rushing touchdowns.
--Field Level Media