Several fungi cause leaf diseases on cottonwood throughout its geographic range. Leaf spot diseases may become epidemic during a wet spring and summer. Although the unsightly leaves and excessive leaf fall can be spectacular, they usually cause only minimal growth loss. A leaf disease is a serious problem only when more than half the leaf surface is infected nor defoliation removes more than half the leaves. Heavy infections for several successive years can predispose the tree to other pathogens, which could cause death.

The most common fungi which cause damage are Taphrina populina Fr., Phyllosticta sp., Cercospora populina E. & E., Colletotrichum gloeosporioides Penz. These fungi overwinter on fallen leaves or twigs. In early spring spores are produced which infect leaves, causing death of leaf tissue. The affected area may be as small as a pinpoint or up to several inches in diameter. It can appear as a spot, ring, blotch, anthracnose. leaf curl, or leaf blister. Often more than one leaf disease is present on a single leaf.