A Lisfranc injury in Locker's right foot will sideline the third-year quarterback for the remaining seven games of the season and thrust veteran backup Ryan Fitzpatrick into the lineup.
"We don't know as far as when and if he'll need surgery and how they will handle that going forward," Munchak said. "But he won't play the rest of the year.
"It's very disappointing, it's hard on the team. ... To lose him now is a huge blow."
Fitzpatrick threw one touchdown and four interceptions when he started two games for an injured Locker earlier this season. The Titans lost to Kansas City and at Seattle.
"Ryan knows he's got to play, we need him to step up," tight end Delanie Walker said. " ... Ryan has no choice but to play good. I feel like he did a great job against the Jaguars. It's his opportunity to be the man now."
Locker had an 87.6 passer rating with eight touchdowns and four interceptions in seven games.
He hurt the foot and he slowed on an option run for an 8-yard gain. He played the next snap, couldn't get wide to Chris Johnson for a stretch handoff and lost a fumble before leaving the game.
The Titans resume their season Thursday night against the Indianapolis Colts at LP Field. Center Brian Schwenke (ankle) and receiver/returner Damian Williams (hip) are day to day but seem unlikely to be able to recover in time for the Colts.