Cruz, 27, sprained his left knee, and also suffered a concussion, in the third quarter of the Giants' game Sunday against the Seattle Seahawks. New York lost 23-0.
While Cruz was cleared from the concussion Wednesday, he underwent an arthroscopic debridement of his left knee. He has been listed as out for Sunday's game against Detroit and will likely miss the Giants' season-ending game against Washington Dec. 29.
Cruz leads the Giants with 73 catches for 998 yards. His four receiving touchdowns are second on the team this season.
Cruz has been with the Giants since the 2010 season and has caught 241 passes for 3,626 yards and 23 touchdowns in his NFL career. He was a Pro Bowl selection in 2012.
The Giants are 5-9 this season and in third placed in the NFC East, three games back of division-leading Philadelphia.
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