Cover crop residues and other biologically based approaches often provide incomplete and inconsistent weed control. This research was conducted to evaluate interactions between hairy vetch residue on the surface of soil and the herbicide metolachlor. Herbicide was applied and incorporated with simulated rainfall before residue placement, residue was applied to the soil surface at precise rates, and potentially confounding variables such as nitrogen and soil moisture were controlled in a greenhouse experiment. Emphasis was placed on the use of suboptimal rates of both residue and metolachlor to explore the potential synergistic interactions between these factors. Deviation from a multiplicative model that included a quadratic response to hairy vetch residue and a log-logistic response to metolachlor was used to demonstrate the presence or absence of synergism. This model effectively showed that emergence of smooth pigweed, common lambsquarters, giant foxtail, and velvetleaf and early growth of smooth pigweed and common lambsquarters were reduced synergistically by the combination of hairy vetch residue and metolachlor. For example, smooth pigweed emergence was reduced 13% by 500 g m−2 of hairy vetch residue alone and was reduced 16% by 10 g ha−1 of metolachlor alone, but together, they reduced smooth pigweed emergence by 86%. This model could be used to determine synergistic interactions between any combination of a phytotoxin and a biologically based weed management approach that could be expressed in quantitative units.