Analysis of grain production performance can provide reference information to explore multiple cropping options and further improve the resource use efficiency of farming methods. This study investigated the spatiotemporal dynamics of grain production performance and efficiency of major crop production systems (CPS) in the Ethiopia’s Blue Nile Basin. The results show that only 39% of the basin is currently cultivated, although a significant cropland expansion (10%) was recorded between 1985 and 2020. The study identified 11 major CPS, mostly practiced in the basin. Of these, single cropping based on the main rainy season (Meher-Only) covers the largest area (26%), followed by Meher-Residual-Intermittent (12%) and Meher-Belg-Dependable (11%). Extended-Meher, Meher-Residual-Dependable, Meher-Residual-Intermittent, and Meher-Belg-Dependable are the four more powerful CPS with higher efficiency. Comparatively, CPS practiced in Wet-Woyna-Dega and Wet-Dega have better overall performance. Findings confirm that agricultural space management (land) and green-water (rainfall) utilization are the most influential factors, followed by land use planning and land use systems (CPS) invention. As landscape suitability for grain production governs future performance, in the low elevation and flood plains parts of the basin, the possibility of creating additional space into the food system is very high. In mountainous and high-altitude regions, the efficiency of grain production will decrease because incorporating additional arable land into the food system is trivial. In the last three decades, in BNB, only 10% of arable land (equivalent to 30 million quintals of food) has been added to the good system, which can support approximately 6 million people. Compared to the population growth of the basin (12 million 1985–2020), its contribution to the food system was less than 50%. This confirms that multiple cropping systems, such as Residual moisture-based CPS, have played a significant role in boosting the food system in the basin. Therefore, improving grain production performance/efficiency requires targeted investments, including the invention of more adaptable crop varieties, efficient cropping practices, and the introduction of advanced agricultural space and water management technologies. The results of the study will help identify important policy gaps and suggest possible options to enhance residual farming and other multiple cropping systems.