Manning completed 24-of-33 passes and wasn't intercepted as the Giants (9-7) piled up a 21-0 halftime lead a cruised to a post-season berth, besting their arch-rivals Dallas in a winner-take-all battle for the division crown in the NFL's final regular-season game.
Victor Cruz made six grabs for 178 yards, including a 74-yard scoring strike from Manning in the first quarter. Ahmad Bradshaw added first-half touchdowns on a 5-yard run and a 10-yard reception for the Giants, who made the playoffs for the first time in three years.
New York grabbed the NFC's fourth seed with the win and will host Atlanta next week.
Tony Romo completed 29-of-37 passes for 289 yards with two touchdowns and an interception for the Cowboys (8-8), who finished the season with four losses in five contests.