Agricultural non-point source pollution is one of the key challenges facing the sustainable development of agriculture in China. A rational cropping system can effectively improve the agricultural ecological environment and enhance the resource utilization efficiency of farmland. To explore a sustainable agricultural model suitable for the red soil area of Hunan Province, this study selected a variety of cropping systems based on the customary fertilization practices of local farmers, using data from 10 national long-term cropland monitoring sites in Hunan Province. The selected cropping systems include four double-cropping rice models: rice-rice-Chinese milk vetch (RRC), rice-rice-barley (RRB), rice-rice-winter fallow (RRW), and rice-rice-rapeseed (RRO); three single-season rice models: rice-tobacco (RT), rice-winter fallow (RW), and rice-rapeseed (RO); and three upland farming models: cotton-rapeseed (CR), soybean-sweet potato (SS), and corn-radish (MR). Using a comprehensive evaluation method of eco-economic benefits, the ecological and economic benefits of the different cropping systems were assessed. The aim was to provide a theoretical basis for the rational layout of cropping systems, improving agricultural productivity, and reducing agricultural non-point source pollution in Hunan Province. The results showed that among the 10 models, the RRC model had the highest composite score of 0.734, followed by the SS model (0.675). The RO and CR models also had relatively high scores of 0.666 and 0.670, respectively. The lowest score was obtained by the RW model (0.392). Therefore, the RRC model is considered the optimal cropping system for balancing both economic and environmental benefits in the red soil area and is recommended for promotion. In contrast, the RW model demonstrated the poorest eco-economic benefits and is not recommended for adoption by farmers.