The Panthers' Graham Gano connected on a 39-yard fied goal to give Carolina a six-point lead with 1:38 left, but Manuel took control from there, marching the Bills on a 9-play, 80-yard drive in the closing seconds.
Buffalo (1-1) evaded a bullet when an apparent interception was nullified by a penalty on Carolina linebacker Luke Kuechly, and Manuel (27-of-39, 296 yards) then sealed the win when found Johnson in the end zone on a 2-yard pass.
The play handed Doug Marrone his first win as an NFL head coach.
Carolina (0-2) got 229 yards, two touchdown passes and one interception from Cam Newton in the loss.
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