The resource utilization of distillers’ grain-derived organic fertilizer is of significant importance for promoting green production of sorghum in Maotai-flavor Baijiu-producing regions and for soil and water conservation on sloping croplands. To determine its appropriate application rate and to clarify its synergistic effects on sorghum growth, soil properties, and soil loss, a runoff-plot experiment was conducted on typical sloping farmland in Renhuai, Guizhou Province. A no-fertilization control (CK) and gradient treatments of distillers’ grain organic fertilizer ranging from 1500 to 10,500 kg ha⁻¹ were established. Responses of sorghum growth, yield components, soil physicochemical properties, aggregate composition, and soil loss were evaluated, and Partial Least Squares Structural Equation Modeling (PLS-SEM) was employed to elucidate the pathways regulating soil erosion. The results demonstrated a pronounced dose–response relationship between distillers’ grain organic fertilizer application and sorghum growth and yield formation. The treatment receiving 6000 kg ha⁻¹ of distillers’ grain organic fertilizer exhibited superior performance in plant height, stem diameter, dry weight per plant, grain dry weight per panicle, and root development. Notably, grain dry weight per panicle and root biomass increased by 307.4% and 130.8%, respectively, compared with CK. Fertilization increased soil organic matter content in the 0–10 cm soil layer and altered the particle size distribution of soil aggregates. Except for the 1500 kg ha⁻¹ treatment, all fertilization treatments reduced total soil loss during the monitoring period. The treatment receiving 9000 kg ha⁻¹ achieved the greatest reduction, decreasing soil loss by 43.8% relative to CK, while the treatment receiving 6000 kg ha⁻¹ reduced soil loss by 38.8%. PLS-SEM results indicated that both root development and yield components were significantly negatively correlated with soil loss. However, the direct effect of fertilization on soil loss was not significant, suggesting that distillers’ grain organic fertilizer primarily reduces erosion risk indirectly by improving soil properties and promoting root development and yield formation. Overall, an application rate of 6000 kg ha⁻¹ of distillers’ grain organic fertilizer for sorghum cultivation on sloping cropland under the conditions of this experiment.