Manningham was listed as doubtful with a knee injury, but joined tight end Jake Ballard, who also missed the game with a knee injury, on the sidelines.
Manningham sat out practice all week long and coach Tom Coughlin said he had swelling in the knee on Thursday. Manningham still said he would play but he was ruled out Sunday morning.
Ramses Barden moved up to being the Giants' third wide receiver.
Bear Pascoe started in place of Ballard. The Giants' other inactives were defensive end Osi Umenyiora (ankle), offensive lineman James Brewer, defensive tackle Jimmy Kennedy, linebacker Mark Herzlich (ankle) and center Jim Cordle.
Jets running back Joe McKnight, the NFL's leading kick returner, was active after being questionable with a separated right shoulder and hyperextended elbow. Defensive back Marquice Cole, who missed last Sunday's game with a knee injury, and defensive lineman Ropati Pitoitua were among the Jets' inactives.
Information from ESPNNewYork.com's Ohm Youngmisuk and The Associated Presscontributed to this report.