Treated effluent from wastewater treatment plants (WWTPs) contains contaminants not fully removed during the treatment process and that may pose environmental health risks when discharged to surface waters. This data release presents inputs for and results from a wastewater reuse model that used data compiled from several sources to calculate the following estimates for each non-tidal, non-coastline, initialized National Hydrography Dataset Version 2.1 (NHDPlus V2) stream segment in the Potomac River watershed: (1) accumulated wastewater as a percent of total streamflow (ACCWW%); and (2) predicted environmental concentrations (PECs, in micrograms per liter) of 69 municipal effluent-derived contaminants. ACCWW% values were calculated for mean-monthly and mean-annual streamflow conditions for both municipal (model results table: Table1_PotomacACCWW_municipal.csv) and industrial-plus-municipal effluent discharges (model results table: Table2_PotomacACCWW_municipal_plus_industrial.csv). PECs were calculated for mean-monthly and mean-annual streamflow conditions for municipal effluent discharges (model results tables: Table3_PotomacPECs.zip, containing comma separated value files of results for mean-monthly and mean-annual conditions). Model estimates at a stream reach of interest represent the combined total upstream wastewater discharges as well as direct discharges into the segment. Model input data included: (1) National Pollutant Discharge Elimination System-permitted facility outfall locations and 2016 average daily effluent discharges linked to a NHDPlus V2 stream Common Identifier (COMID) and facility-specific information on treatment levels and population served per capita (model input table: Table4_PotomacWWTPs.csv); (2) NHDPlus V2 stream geometry and hydrologic attributes (hydrosequence, startflag, terminalfl, divergence, fromnode, tonode, and Enhanced Runoff Method mean-monthly and mean-annual gage-adjusted streamflow and velocity, 1971-2000) (model input table: Table5_PotomacNHDPlusV2.1_flowlines_hydrology.csv); and (3) contaminant-specific data on consumption, fate, and transport compiled from literature sources or estimated from physicochemical properties (see: supplementary table in Larger Work Citation). In Table 4, where information on population served by the facility was missing, this value was estimated by standardizing to 100 gallons per capita per day. Information on population served was only acquired and estimated for municipal facilities. Where treatment level information was missing, the treatment level was assumed to be primary. Ninety-two percent of WWTPs have an assumed treatment as none was reported. R (version 4.0.4) and Python (version 2.7.16) scripts were used to summarize wastewater inputs from outfall locations by COMID and route and accumulate each wastewater and predicted contaminant loads while accounting for in-stream dilution and attenuation of contaminants. Any users of these data should review the entire metadata record and the associated manuscript (see Larger Work Citation). See 'Distribution liability' statements for more information.