Sassafras is found throughout the eastern and southern United States, and into Mexico. It ranges as far west as Texas and Iowa. It grows well in moist, well drained, or sandy loam soils but may tolerate a variety of soil types. It is commonly found in open woods, along fences, or in fields.

Sassafras trees regenerate quickly after a disturbance, and are early pioneers in old fields. This species is sometimes grown to restore depleted soils.