Martin stayed on one knee after a 7-yard run by running back Rod Smith. Athletic trainers escorted him to the blue medical tent on the sideline, and after about 10 minutes, Martin exited with a noticeable limp.
Martin headed into the locker room after speaking to Frederick and other teammates on the sideline.
It appeared he may have taken a helmet to the knee, and the Cowboys announced a knee injury for Martin.
He was replaced by Kadeem Edwards.
The Cowboys already lacked depth with backup guard Joe Looney starting at center with Frederick dealing with stingers. Backup guard Marcus Martin will spend the season on injured reserve after tearing a ligament in his right big toe in the preseason opener.
Zack Martin signed a new deal in June that made him the highest-paid guard in the league. He has made the Pro Bowl every year since entering the NFL in 2014.