Populus deltoides is one of the largest North American hardwood trees. Male and female flowers are born on separate trees.

Eastern cottonwood is often grown for plywood and interior parts of furniture. Due to the flat stem of the leaf, the leaf has the tendency to shake from even the slightest breeze.

This species has some wildlife value. Seedlings and young trees are browsed by rabbits, deer, and domestic stock. Beavers use saplings and poles for food and dam construction.