Desertification, climate variability and food security are closely linked through drought, land cover changes, and climate and biological feedbacks. In Ghana, only few studies have documented these linkages. To establish this link the study provides historical and predicted climatic changes for two drought sensitive agro-ecological zones in Ghana and further determines how these changes have influenced crop production within the two zones. This objective was attained via Markov chain and Fuzzy modelling. Results from the Markov chain model point to the fact that the Guinea savanna agro-ecological zone has experienced delayed rains from 1960 to 2008 while the Sudan savanna agro-ecological zone had slightly earlier rains for the same period. Results of Fuzzy Modelling indicate that very suitable and moderately suitable croplands for millet and sorghum production are evenly distributed within the two agro-ecological zones. For Ghana to adapt to climate change and thereby achieve food security, it is important to pursue strategies such as expansion of irrigated agricultural areas, improvement of crop water productivity in rain-fed agriculture, crop improvement and specialisation, and improvement in indigenous technology. It is also important to encourage farmers in the Sudan and Guinea Savanna zones to focus on the production of cereals and legumes (e.g. sorghum, millet and soybeans) as the edaphic and climatic factors favour these crops and will give the farmers a competitive advantage. It may be necessary to consider the development of the study area as the main production and supply source of selected cereals and legumes for the entire country in order to free lands in other regions for the production of crops highly suitable for those regions on the basis of their edaphic and climatic conditions.