The North Fork Holston River (NFHR) historically supported 33 unionid mussel species downstream of Saltville, VA. Because of industrial contamination over decades from a chlor-alkali plant, a U.S. Environmental Protection Agency Superfund Site (SITE) was created with Hg and MeHg designated as contaminants of concern. Mussel surveys were conducted at 18 NFHR locations to determine abundance, species richness, and recruitment upstream and downstream of the SITE. Seventeen unionid species were collected, and mean species richness of upstream sites (8.8 species, n = 6 sites) was greater than the mean of downstream locations (3.8 species, n = 12). The catch-per-unit-effort mean from upstream sites (10.4 mussels/h, n = 3 sites) was greater than the mean of downstream sites (3.5 mussels/h, n = 12). Mean density of upstream (1.8 mussels/m², n = 6 sites) sites was higher than observed at downstream (1.0 mussels/m², n = 8) locations. Results show that species richness in the entire lower NFHR is less than observed upstream, and measures of mussel abundance and recruitment also are severely depressed in the ∼35 km reach downstream of the SITE, where no juvenile and very few adult mussels were collected. The influences of a wide array of contaminants, including Hg, MeHg, Cl^-, major ions, and trace elements, from the SITE on downstream recovery of unionid mussels are discussed.