Lions coach Jim Caldwell told reporters in Allen Park, Michigan, on Monday that the team will place Pettigrew on injured reserve.
With Pettigrew out for the season, the Lions have only two tight ends on the 53-man roster: Eric Ebron and Tim Wright.
Pettigrew caught seven catches for 67 yards and one touchdown this season; he had been Detroit's primary blocking tight end.
This isn't Pettigrew's first major left knee injury. His rookie season in 2009 ended on Thanksgiving after he tore the ACL in his left knee -- the same knee he hurt Sunday against the Rams.
Pettigrew was the second draft pick of former general manager Martin Mayhew after No. 1 overall pick Matthew Stafford. The Lions took Pettigrew in the first round in 2009.