The objective of this study is to understand how soil microorganisms interact with cover crop-derived allelochemicals to suppress weed germination and growth following cover crop residue incorporation. We conducted a time series experiment crossing sterilized and non-sterilized soil with four different residue treatments. We measured weed seed germination rates, radicle elongation, and disease incidence in seed germination bioassays. We also monitored cover crop-derived, isoflavone allelochemicals in these bioassays. We partitioned the total weed suppression into three sources: microbe-only inhibition, residue-only inhibition, and the microbe-residue interaction. Microbial activity suppressed weed germination and growth for 30 days, while cover crop-derived allelochemicals provided suppression for a limited time. There was an antagonistic interaction between microbes and allelochemicals. This interaction was strongest for water-soluble allelochemicals, while residue fractions containing intact plant tissues retained greater suppressiveness even in the presence of a live microbial community. Microbial activity can directly suppress weed germination and growth, but microorganisms also indirectly help weeds by degrading cover crop-derived allelochemicals. As a result of these interactions, cover crop-derived weed suppression in agricultural soils shifts from an early allelochemical-dominated phase to a later phase where microbial suppression is more important.