This species is native to eastern North America, where its range includes much of the Mississippi River system.

[3] In Canada the mussel is limited to Ontario, where it only remains in the Sydenham and Ausable Rivers and Lake Saint Clair.

[2] The larvae, or glochidia, of Unionidae are known to use the gills, fins, or skin of a host fish for nutrients during their development.

Ptychobranchus fasciolaris enclose their glochidia in a membranous capsule called a conglutinate that resembles an insect larva or small fish.

When a host fish bites the capsule bait, the Ptychobranchus fasciolaris glochidia attach to its gills, where they feed.