The Bucs lost 48-3.
McCoy's left leg bent back violently while defending a running play late in the first quarter. He lay on the ground for several minutes before limping off the field with the help of team trainers.
The former Oklahoma star was selected third overall by the Bucs in 2010, making him the franchise's highest-drafted interior lineman since they took Warren Sapp 12th overall in 1995. McCoy finished with three sacks and 22 tackles in 13 games as a rookie.
He began Sunday with one sack and 10 tackles through four games this season.
Information from The Associated Press contributed to this report.