The 2017 first-round pick was injured defending Lions tight end Jesse James early in the second quarter. He remained on the Ford Field turf while trainers evaluated his right leg, then walked to the Bills sideline under his own power.
Buffalo trainers wrapped White's leg on the sideline, and he was officially ruled out minutes into halftime.
White was the Bills' second starter to exit the team's third preseason game, after left guard Quinton Spain left late in the first quarter with an ankle injury.
Levi Wallace, Buffalo's starting cornerback opposite White, briefly came off the field after the wind was knocked out of him, but he later returned.
The 27th overall draft pick in 2017, White was a Pro Football Focus Second-Team All-Pro during his rookie season. He has started in all 32 possible games of his career.
Bills coach Sean McDermott originally planned to play his team's starters into the third quarter but abandoned that strategy, sending out the second-string offense and defense to start the second half.