Sustainable cropping systems that balance agricultural productivity and ecological integrity are urgently needed. Overreliance on soil tillage and herbicides to manage weeds has resulted in a number of major environmental problems including soil erosion and degradation, biodiversity loss, and water quality impairment. Combining organic farming and conservation agriculture is a viable alternative to address these challenges. In particular, mulch-based no tillage systems can be used to reduce tillage in organic production, improving soil quality while decreasing labor and fuel requirements. This technique involves planting cash crops directly into terminated cover crops that remain on soil surface and serve as mulch to prevent weeds establishment and protect soil from erosion. Despite potential benefits, adoption of organic mulch-based no tillage is limited due to challenges with cover crop termination, weed suppression, and yields. Here, we (i) review international research on organic mulch-based no tillage systems (soybean and maize), (ii) identify production issues that limit the success of this technique, and (iii) outline research priorities. As result, organic mulch-based no tillage is knowledge intensive and requires advanced planning and careful management of the cover crop. Primary challenges include timely cover crop establishment and termination, nutrient management, reduced soil temperature and moisture at planting, and achieving adequate seed-to-soil contact when planting into thick mulch on soil surface. Long-term research is needed to better understand the effects of this technique production on soil health and on the broader environmental and economic impacts. To increase adoption of organic mulch-based no tillage, future research should focus on (i) screening species and cultivars to identify cover crop and crop combinations that optimize cropping system performance and (ii) developing equipment for improving cover crop termination and seed placement. Research conducted in partnership with farmers will be valuable for developing guidelines and increasing adoption of this technique.