Interseeding alfalfa (Medicago sativa L.) into corn (Zea mays L.) is a novel approach that increases the production of high-quality forage and reduces the risk of nutrient and soil loss from cropland. Annual grass weeds like yellow foxtail [Setaria pumila (Poir.) Roem. & Schult.] can reduce the success of alfalfa establishment and are difficult to manage in the interseeding system. This study evaluated ground cover, fall biomass, and fall plant density of interseeded alfalfa in response to varying populations of S. pumila. Our goal was to identify a threshold for initiating control of annual grasses to ensure good establishment of alfalfa in this intercropping system. Ground cover of interseeded alfalfa growing under corn declined as S. pumila density increased from 0 to 125 plants m−2 in July, August, and October with the sharpest decline in August (up to a 70% reduction in alfalfa cover). This reduction in ground cover was associated with a decline in postestablishment shoot and root mass and a reduction in alfalfa plant density from 246 to 146 plants m−2 in October. Results suggest that June S. pumila populations should be kept to less than 50 plants m−2 to obtain recommended fall alfalfa densities of 200 plants m−2 that are needed to maximize alfalfa yield the following year. This research provides crucial information to practitioners on when annual grass management is needed to ensure successful alfalfa establishment in this interseeded system.