Knight had 21 points before hyperextending his right knee late in the third quarter with the Pistons up by three.
Monroe stepped up and delivered, scoring 10 of his 19 points in the fourth quarter as the Pistons earned a much-needed 105-99 win over the Charlotte Bobcats on Wednesday night.
"He had his momentum going down the stretch," said Bobcats guard Ramon Sessions. "It's tough to stop a player like him when he's playing the way he did."
Calderon finished with 17 points, including two key free throws to seal the game with 21 seconds left.
Monroe and Calderon accounted for Detroit's final 15 points.
The Bobcats are now 20-100 since the start of the 2011-12 season.
The Pistons led 77-74 with 1:45 left in the third quarter when Knight was tripped up by Bobcats point guard Kemba Walker after Walker lost control of the ball in the lane. Walker was called for a foul and Knight remained on the court for several minutes before getting up and gingerly walking to the bench.
Knight would return briefly in the fourth quarter for one possession before injuring his ankle because he was overcompensating for his injured knee.
At that point, Knight walked to the bench with a noticeable limp and did not return.
Knight said he wanted to continue. He's uncertain if he'll play Friday night at Indiana.
"You've got to listen to your body sometimes, but as a competitor when your team is in a close game, you always want to play, especially when you have an opportunity to put a team away," Knight said. "As long as we won, I'm happy. That's what I'm most happy about."
The Pistons can thank Monroe for that.
The second-year center muscled his way into the lane for some key baskets late in the game against the less physical Bobcats.
"We all stepped and played well tonight," Monroe said. "We got into attack mode tonight. They drew up some plays for me in the post tonight. I just tried to make the right decision and took advantage of some one-on-one action and was able to make some plays at the rim."
Walker led all scorers with 24 points but had five turnovers.
Sessions had 18 points and eight assists off the bench for the Bobcats and Byron Mullens added 15 points.
The Bobcats cut the Pistons' 11-point lead to one late in the fourth quarter before Monroe scored on a spin move inside. Calderon put away the game with a pair of free throws with 21 seconds left after Mullens missed a jumper and Walker turned the ball over at the top of the key.
The Pistons were coming off a 14-point loss to the Memphis Grizzlies on Tuesday night, a defeat that coach Lawrence Frank called "a real stinker."
He felt better about this one, calling it a "gritty win."
"It was a good result," Frank said. "We got off to a good start, which always helps. We executed well down the stretch. Showing our execution down the stretch. Our patience, our poise and playing through a little bit of adversity."
The Bobcats entered the fourth quarter down 78-77 but the Pistons quickly built a double-digit lead after Kyle Singler scored off an offensive rebound with seven minutes left in the game.
The Bobcats clawed back behind a pair of 3-pointers from Mullens and two nasty dunks by rookie Michael Kidd-Gilchrist but couldn't seize the lead.
Charlotte dropped to 7-20 at home and 13-41 overall.
"Our biggest problem was defensively, we weren't able to get stops," Walker said. "We missed a lot of rotations and weren't talking to each other. We weren't in sync tonight. We've got to get that back."
Detroit hasn't looked sharp on the road, carrying a 6-18 record into the game. But the Pistons looked good early, jumping out to an 11-point first-quarter lead behind 11 points from Knight and three 3-pointers from Calderon.
Rodney Stuckey added 12 points and tied a season-high with seven rebounds off the bench for the Pistons.
Carolina Panthers wide receiver Steve Smith took in Wednesday night's game. ... Tyrus Thomas, one of Charlotte's highest-paid players, was inactive for the fourth straight game. ... Walker has now topped 20 points in a game 18 times this season. ... Monroe tied a career high with three blocks.