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Climate change and variability pose a serious threat to food production in sub-Saharan Africa. The projected changes in local spatio-temporal patterns of rainfall and temperature will likely affect the availability of water and nutrients, crop growth, and yield formation. This paper presents the simulated effects of climate change on maize (Zea mays L.) in Ejura in the Sekyedumase district of Ghana, one of the important food baskets of the country. Experimental data from maize grown under various nitrogen (N) and phosphorus (P) conditions in the 2008 major and minor rainy seasons at two sites in Ejura were used to parameterize and evaluate the cropping systems model APSIM. Daily climatic data for the period 2030-2050 under the scenarios A1B and B1 were obtained from the regional climate projections obtained by the mesoscale model MM5. The assessment of climate change impact on grain yield suggested a likely 6-week shift in the planting dates of the rainy season from the current (1980-2000) 3rd week of March to the 2nd week of May for the simulated period. Climate change also resulted in projected yield reduction of, on average, 19% and 14% for the Obatanpa maize variety under A1B and B1, respectively, for maize-maize continuous cropping. Likewise, the Dorke maize yield is expected to reduce by 20% and 18% for A1B and B1, respectively, with increased yield variability under both scenarios. Potential adaptation measures to climate change in the area include cropping of cowpea during the minor season or fallow rotation with other crops.