Cover crops (CCs) have shown great potential for suppressing annual weeds within agronomic cropping systems across the United States. However, the weed suppressive potential of CCs may be moderated by environmental and management factors that are specific to certain geographic areas and their associated characteristics. This may be particularly true within the U.S. Southeast, where higher mean annual temperature and precipitation generate favorable conditions for both CC and weed growth. To understand the effects of this regional context on CCs and weeds, a meta-analysis examining paired comparisons of weed biomass and/or weed density under CC and bare ground conditions from studies conducted within the Southeast was conducted. Data were identified and extracted from 28 journal articles in which weed biomass and/or weed density were measured along with cash crop yield data, if they were provided. Fourteen studies provided 142 comparisons for weed biomass; 23 studies provided 139 comparisons for weed density; and 22 studies, pooled over both weed response variables, provided 144 comparisons for cash crop yield. CCs had a negative effect on weed density (P = 0.0016) but no effect on either weed biomass (P = 0.16) or cash crop yield (P = 0.88). The mean relative reduction in weed density under CCs was 44%. Subsequent analyses indicated that CC biomass was the key factor associated with this reduction. Weed density suppression was linearly related to CC biomass; a 50% decrease in weed density was associated with 6,600 kg ha−1 of CC biomass. Edaphic, geographic, and other management factors had no bearing on this suppressive effect. This highlights the importance of generating adequate CC biomass if weed suppression is the primary objective of CC use and the potential for CCs to reduce weed density over diverse soil, climate, and farm management conditions.