The decline in soil fertility is a fundamental impediment to agricultural growth and a major reason for food insecurity in Sub-Saharan Africa. This study aimed to identify the best management practice applicable to organic manures (OM) and inorganic fertilizers (IF) for sustainable production. It was conducted in 2018-2019 in Burkina Faso using a Randomized Complete Block Design with six treatments in three replications. The applied treatments were: T1 (control); T2 (simple compost), T3 (Piliostigma reticulatum leaves compost), T4 (T2 + ½ IF), T5 (T3 + ½ IF) and T6 (IF). The effects of these treatments were evaluated on soil properties (C, N, P, K) and sorghum grain yield using XLSTAT version 2014.5.03 software. The results showed that the incorporation of O Min soil increased significantly soil pH and its properties. The combined application of OM with IF decreased soil properties but it contributed to increase significantly sorghum yield specifically under the combined application of simple compost with IF. Under an exclusive use of IF and the control plot, soil C decreased with consequent decline in soil pH and nutrients content. Also, under the combined incorporation of P. reticulatum compost with IF, sorghum yield decreased. Therefore, appropriate application of inorganic and organic fertilizers is needed to increase soil organic matter and maintain its productivity