Stewart was blocking on a 26-yard running play by Chris Johnson when Texans linebacker Barrett Ruud rolled into his right leg. Trainers put an air cast on Stewart's lower right leg, while a cart quickly came out to pick him up.
He was taken into the locker room for observation, and officials later announced Stewart had a broken leg. Mike Otto replaced Stewart.
The right tackle had started 103 games since being drafted in 2005.
The Titans had a second offensive lineman hurt in the first half when left guard Steve Hutchinson injured his right knee, and his return was questionable.