The leaf is very coarsely toothed, the teeth are curved and gland tipped, and the petiole is flat; they are dark green in the summer and turn yellow in the fall (but many cottonwoods in dry locations drop their leaves early from the combination of drought and leaf rust, making their fall color dull or absent).

[10] The subspecies classification is as follows: It needs bare soil and full sun for successful germination and establishment; in natural conditions, it usually grows near rivers, with mud banks left after floods providing ideal conditions for seedling germination; human soil cultivation has allowed it to increase its range away from such habitats.

[8] Unlike related species such as quaking aspen, it does not propagate through clonal colonies, but will resprout readily when cut down.

The wood of eastern cottonwood is typical of the Populus family in its softness, weighing just 0.45 g/cm3 (28 pounds per cubic foot).

General Custer fed his horses and mules the bark during the 1868–69 winter campaign against Native American tribes south of Arkansas.

The Balmville Tree (felled in 2015 at approximately 316 years old) was the oldest eastern cottonwood in the United States.