Herbicides are widely applied along highways to control roadside vegetation, and surface water is frequently nearby. To determine whether herbicide runoff along highways threatens water quality, a field study was conducted at two sites in northern California for three rainy seasons. The herbicides oryzalin, isoxaben, diuron, glyphosate, and clopyralid were selected for study to include compounds with significant variation in physical/chemical properties. Concentrations of herbicides in runoff were monitored for up to 11 storms following herbicide application, and 24 samples were collected per storm, providing unprecedented temporal detail. Flow-weighted event mean concentrations were calculated for each herbicide in each storm and ranged from below detection limits to 43.13 μg/L for oryzalin. The least soluble compounds, isoxaben and oryzalin, were detected in all storms monitored while the more soluble compounds, diuron and clopyralid, declined to levels below detection limits before monitoring was concluded. Very small amounts of glyphosate were mobilized, but its transformation product aminomethylphosphonic acid was detected at higher concentrations, in more storm events, and at greater depth in the soil profile. A first-order model successfully described the declining herbicide concentrations in spray zone soil and in surface runoff for all sites and herbicides. Fitted first-order coefficients were always higher for runoff than for soil, indicating that the herbicide that persists in the source zone becomes less available for runoff as the time since application increases. The percentage of the applied herbicide that was detected in surface runoff over a season ranged from 0.05% to 43.5%, and the most critical variables in controlling the variation were the solubility of the herbicide and the runoff volume. For a given herbicide and site, the most critical factors in determining seasonal herbicide loss to surface waterwere the timing and intensity of the first storm following application, affecting total seasonal runoff by up to 2 orders of magnitude. Minimizing runoff of herbicides along highways will thus require careful attention to the intrinsic mobility of the compound and the timing of its application.