They are carnivorous, and prey primarily on insect larvae, crustaceans, and fishes. Field studies show that small sculpins prefer mayfly nymphs and small worms. Larger individuals tend to eat caddisflies, crayfish, larger worms, etc. Smaller sculpins are quite commonly eaten by larger individuals in this highly cannibalistic species. Eggs are also cannibalized during the breeding season.
Mottled sculpins breed in early spring.
The breeding season begins when adult males occupy cavities beneath rocks on the streambed. Males darken considerably so that their heads become jet black and their dorsal fins become outlined in reddish-orange. Males are pugnacious during the breeding season, and defend their burrows from any intruders. During this period, females swell with eggs. Fully gravid females look as though they will burst, and the outline of the individual eggs may be seen through the tightly stretched abdominal wall.