The injury occurred in the first half Monday night. Team officials declined to specify which ankle.
Umenyiora came into the game ranked second on the Giants in sacks with seven. He was credited with only one assisted tackle against the Saints, who raced to a 21-3 halftime lead while not allowing a sack on quarterback Drew Brees.
Giants officials initially said Umemyiora was probable to return, but early in the second half he was listed as out for the remainder of the game.
New York wide receiver Hakeem Nicks left in the third with bruised ribs but returned before the end of the quarter.