The Northern Short-tailed Shrew is realtively large and robust, with inconspicuous ears and minute eyes. The snout is pointed and somewhat proboscis-like but relatively shorter and thicker than in other shrews. They are among the largest North American shrews, weighing up to 1.1 ounces, with a body 3 to 4 inches long. Active all year, day or night, short-tailed shrews forage in leaf litter and fallen grass for invertebrates (primarily earthworms, slugs, snails, and insects), and they pursue small salamanders, reptiles, and mice. Their saliva contains a neurotoxin and a hemotoxin that are introduced into a wound by chewing. These toxins are used primarily to immobilize mice and invertebrates, especially snails, which are stored for later use.

Northern Short-tailed Shrews are most common in hardwood forests with deep leaf litter and in brushy sites adjacent to ponds and streams, less common in conifer forest and grassland. Short-tailed shrews travel on the ground, using runways through surface litter and snow. Most of their time, however, is spent underground in burrows they excavate or in those constructed by moles or voles. Burrows are usually 10 cm below the surface but can be 50 cm deep. Within tunnel systems, territories are marked by odorous secretions from scent glands on the body, as sight is restricted to light detection. The shrew uses a large repertoire of squeaks, clicks, twitters, and ultrasonic sounds to navigate and to locate prey via echolocation.