Newton made good on 15-of-27 pass attempts for 223 yards and three touchdowns with an interception, while adding 45 rushing yards with a score on the ground.
On defense, the Panthers allowed just 10 first downs and tied a team record by sacking Giants quarterback Eli Manning seven times.
The Giants (0-3), meanwhile, remained winless after three games for the first time since 1996.
Manning managed to complete just 13-of-24 passes for 128 yards and was intercepted once in the loss.
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