The American Toad is common throughout most of its geographic range, which includes the southeastern Canadian provinces and most of the eastern half of the United States. It is absent from the warmest parts of the southeast. In Nebraska, it reaches the extreme western edge of its range and is restricted to only a few of the eastern-most counties. It is known from Washington, Douglas, and Sarpy counties but also may occur as far south as Richardson County. This toad is listed as a species in need of conservation (SINC) in Nebraska due to its limited distribution in the state. It is known to hybridize with Woodhouse’s Toads (Anaxyrus woodhousii) in Nebraska in areas where their ranges overlap.

In Nebraska the American Toad inhabits riparian woodlands and deciduous forests associated with the Missouri River. Heavily canopied lowland forests and hillsides with permanent to semi-permanent marshes or ponds in the vicinity are preferred habitats. Temporary and permanent wetlands provide spring breeding habitat. They are active from mid-April through October in Nebraska. American Toads are mostly nocturnal and are more active on warm, humid evenings. Rainy nights in spring and summer stimulate males to migrate to wetlands and start vocalizing to attract females, although females only respond and breed during mid-spring. The voice of the American Toad is a long, musical trill that lasts up to 30 seconds. Long strings of gelatinous eggs are laid in shallow water, and tadpoles – like the other Anaxyrus tadpoles in Nebraska – are small, black, and non-descript.