Benjamin was carted off to the locker room after being evaluated in the medical tent. He was taken from the tent to the cart with assistance from Bills medical staff.
The injury occurred after Benjamin caught a 20-yard pass from rookie quarterback Nathan Peterman, making his first career start after Tyrod Taylor was benched. Benjamin caught the pass over the middle of the field and then was hit in his right knee by Chargers safety Adrian Phillips, causing his leg to bend backward.
Benjamin remained on the ground for several moments before walking slowly to the medical tent flanked by members of the medical staff.
The Bills acquired Benjamin in a trade Oct. 31 from the Carolina Panthers for third- and seventh-round picks in 2018. He made his debut Nov. 12 against the Saints, making three catches for 42 yards.
Benjamin is under contract with the Bills through 2018 under the fifth-year option the Panthers exercised in his deal. The option, which will pay $8.5 million, is guaranteed for injury.