Least weasels are just as aggressive and predatory as the larger weasels and kill in the same manner. If disturbed near its nest, an adult least weasel will chirp at its enemy. When agitated, they spray musk from their anal scent glands. The species preys on mice, voles, small birds, insects, earthworms and small amphibians. Sometimes they kill more than they can eat and cache uneaten prey in their dens.
Least weasels breed and reproduce year-round, with the possible exception of winter.
Delayed implantation does not occur, and two or more litters may be produced each year. A female's estrus lasts four days. Young are blind and naked, but develop rapidly. Immatures reach adult length after about eight weeks, and adult weight when 12-15 weeks old. Females mature sexually in four months, males in eight.