Nerodia sipedon is banded, dark, blunt-headed and bad-tempered when cornered, flattening its head and striking repeatedly. That combination reads as danger, and the species is destroyed on sight across much of its range.
The distinguishing marks are consistent. A cottonmouth has a vertical pupil, a heat-sensing pit between eye and nostril, and a facial scale arrangement that gives it a heavy angular brow; a water snake has a round pupil, no pit, and a more tapered head. Cottonmouths tend to swim with the body riding high and buoyant on the surface, while water snakes swim mostly submerged with the head above. Cottonmouths also gape to display a white mouth lining, which water snakes do not do.
Range is decisive. The cottonmouth does not occur in Canada, New England, New York, Michigan, Ohio or most of the upper Midwest, so any snake in the water in those places is not one. Killing water snakes is also counterproductive: they take large numbers of sick and slow fish and are an ordinary part of a functioning freshwater system.