Stormwater practitioners need quantitative information about the quality and volume of highway runoff to assess and mitigate potential adverse effects of runoff on the Nation’s receiving waters. The U.S. Geological Survey developed the Highway Runoff Database (HRDB) in cooperation with the FHWA to provide practice-ready information to meet these information needs on the local or national scale. This paper describes the datasets that are available in version 1.1 of the HRDB and demonstrates how data and statistics from the HRDB can be used with the Stochastic Empirical Loading and Dilution Model (SELDM) to simulate highway runoff. The HRDB includes 249 sites, 6,849 runoff events, and 106,869 event mean concentrations (EMCs) collected during the 1975–2017 period. It includes data from 16 States in the conterminous United States and from Hawaii. The EMCs in the HRDB include measurements for 415 different water-quality constituents. These water-quality measurements include 32,944 trace-metal; 27,496 organic; 15,684 nutrient; 13,016 physical property; 10,307 major inorganic; 6,773 sediment; and 649 other constituent values. There are large variations in the data. For example, EMCs for total suspended solids and total phosphorus range from 0.4 to 5,440 mg/L and 0.004 to 22 mg/L, respectively; geometric means range from 1.58 to 1,379 mg/L and 0.017 to 2.82 mg/L for these constituents, respectively. The example simulations indicate that risks for adverse effects of runoff can vary by orders of magnitude; the HRDB and SELDM facilitate selection of representative statistics from available datasets.