John Smith's circa-1608 map as Mataughquamend, an Algonquian compound translated as “where one goes pleasantly.”[2] Today, Mattawoman Creek is listed by the Environmental Protection Agency (EPA) as impaired under Section 303(d) of the Clean Water Act for excess nutrients, sediment, and loss of living resources.

The largemouth bass, a resident gamefish that supports an active recreational fishery in the tidal freshwater Potomac River and its tributaries, also achieves high concentrations in the estuary.

Palustrine wetlands are concentrated in the broad stream valley of the fluvial reaches, where a site with the greatest species richness of amphibians and reptiles in Maryland has been identified by the Department of Natural Resources.

Its watershed remains over 50% forested, but it is approaching a 10% impervious cover,[11] often cited as a threshold for significant degradation as measured by water quality and species diversity.

With respect to projected growth, the Mattawoman Creek Watershed Management Plan authored by the U.S. Army Corps of Engineers notes that[11] [t]hese intense development practices would have severe repercussions on the biological community and would decrease the habitat quality within the estuary.