The cropping systems model APSIM (Agricultural Production Systems sIMulator) was applied to assess the response of sorghum grain yield to inorganic fertilizers applications and residue retention in diverse farmers’ management systems (homestead fields and bush farms). The model was parameterized using data collected from experiments under optimum growth conditions (limited water or nutrient stress). Independent data from field experiments with three levels of P and four levels of N fertilizers conducted at two different locations and soils were used to evaluate the model. Soil water and fertility parameters measured were used for simulations while same starting conditions were assumed for unmeasured parameters for all trials. APSIM predicted the grain yield response of sorghum to both N and P applications with an overall modified internal coefficient of efficiency of 0.64. Following model parameterization, a long-term simulation study was conducted using a stochastic weather data derived from historical weather data to assess the effects of crop residue management on grain production. A gradual decline in sorghum grain yield was simulated over the 30-year simulation period in both the homestead fields and the bush farms, with yields being much lower in the latter under farmers’ management practices. Half the amount of mineral N fertilizer used in the bush farms was needed in the homestead fields to produce the average grain yields produced on the bush farm with full fertilization, if crop residues were returned to the fields in the homestead. Year-to-year variability in grain yield was consistently higher with the removal of crop residues, irrespective of management systems. APSIM was responsive to both organic and inorganic fertilizer applications in the study area and also highlighted the essential role of crop residues and inorganic fertilizer in influencing the temporal sorghum grain production and hence the impact of farmers’ management practices on food security. This was evident in the rapid decline in soil organic carbon (SOC) accompanied by a decline in grain yield over the 30 years of cropping. The use of inorganic fertilizer and retention of crop residues (SOC) are critical for attaining food security in the study area.