Climate variability, the short-term fluctuations in average weather conditions and agriculture affect each other. Climate variability affects the agro ecological and growing conditions of crops and livestock, and is believed to be the greatest impediment to the realisation of the first Millennium Development Goal of reducing poverty and food insecurity in arid and semi-arid regions of developing countries. Conversely, agriculture is a major contributor to climate variability and change by emitting greenhouse gases and reducing the agro ecology’s potential for carbon sequestration. What however, is the empirical evidence of this inter-dependence of climate variability and agriculture in Sub-Sahara Africa? In this paper, we provide some insight into the long run relationship between inter-annual variations in temperature and rainfall versus annual yields of the most important staple food crops in Northern Ghana. Applying pooled panel data of rainfall, temperature and yields of selected crops from 1976 to 2010 to co-integration and Granger causality models, there is cogent evidence of co-integration between seasonal, total rainfall and crop yields; and causality from rainfall to crop yields in the Sudano-Guinea Savannah and Guinea Savannah zones of Northern Ghana. This suggests that inter-annual yields of the crops have been influenced by the total mounts of planting season rainfall. Temperature variability over the study period is however stationary, and is expected to have minimal effect if any on crop yields. Overall, the results confirm the fitness of our model of long-term relationships between climate and crop yield variables, and have implications for production decisions on croplivestock integration by smallholder farming systems.