With the exception of a few populations in the Tonawanda Creek drainage of western New York, all known and historical populations are located along the Hudson River. There are historical records from New York City to the Castleton Bridge. Today, extant populations along the Hudson River are only known within freshwater tidal areas from the Rondout Creek mouth northward towards Troy.

Heartleaf plantain is characterized by a widespread geographical range within which it is highly localized. A high proportion of the populations are located along the Hudson River, but populations range from New York, south to Virginia, North Carolina, Georgia, and Alabama. It is disjunct inland to Ohio, southern Ontario, Wisconsin, and south through the Mississippi Valley.