Minnesota quarterback Tavaris Jackson passed for 129 yards and a touchdown and rushed for another 38 yards.
Jackson and Sidney Rice hooked up on a 60-yard TD pass, helping the Vikings run up a 24-7 lead by halftime.
Chester Taylor ran for 77 yards and a score for Minnesota.
Manning completed 21 of 49 passes and one touchdown.
The Giants (7-4) fell three games behind Dallas in the NFC East.
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