Maize (Zea mays L.) is an important food crop in Kenya, while low and erratic rainfall, and low nutrient input mainly result in low maize yield. This study were to assess optimal nutrient and irrigation management practice for maize in central Kenya based on field experiment combined with modeling simulation. On-farm experiment with four treatments including no fertilizer (N0), N applied at dose of 100 kg ha(-1) only in the form of a chemical fertilizer (N100) or combined with animal manure (N100M) or straw (N100S) has been conducting since 2013 in central Kenya. The Decision Support System for Agro-technology Transfer-Cropping System Model (DSSAT-CSM) was firstly calibrated under the relative optimal treatment N100M, and it was then evaluated for the rest three treatments for 6 maize growing seasons from 2014 to 2018. The responses of grain yield to different irrigation and fertilizer regimes were simulated using the calibrated DSSAT-CSM. The combination of fertilizer and manure (N100M) resulted in the highest yield and that of fertilizer and straw (N100S), in the highest level of soil water content in each soil layer. The model (DSSAT-CSM) successfully predicted both grain yield (normalized root mean square error, or nRMSE, of 21-37% and the index of agreement, or d, of 0.89-0.93) and changes in water content of each soil layer (nRMSE < 20% and d > 0.70) in all treatments except N100S. The yield was most sensitive to any deficit in soil water content (dry spells) at the beginning of grain-filling stage, and the best regime for high yield, high water-use efficiency, and high agronomic efficiency comprised irrigation at 50-70 mm during that stage combined with fertilizer N at 100-120 kg ha(-1). The estimated magnitude yield gain with respect to optimal nutrition and irrigation ranged from 2 to 4 t ha(-1) in different crop seasons. Optimal application of irrigation at the sensitive stage, fertilizer N, animal manure, and straw mulching holds great potential as an integrated farming practice for high grain yield and for efficient use of resources in maize cultivation in semi-arid parts of Kenya.