According to the majority of regional climate projections, Sub-Saharan Africa (SSA) will likely become warmer in the next decades and rainfall patterns will substantially shift. Understanding the effect of climate variability on food security and poverty and identifying effective adaptation measures in the context of subsistence agriculture is imperative to ensure food security now and in the future. This article presents a micro-level simulation study that was undertaken for Northern Ghana, building on the approach and data developed within a research project of the CGIAR Challenge Programme on Water and Food. The study applied agent-based modelling to analyse how adaptation affects the distribution of household food security and poverty under current climate and price variability. Specifically, we examined the effectiveness of policy interventions related to the promotion of agricultural credit and off-farm employment opportunities. Our simulation experiments suggest that both climate and price variability have a pronounced negative effect on household welfare. Moreover, we found substantial difference in the poverty and food security status of households due to climate and price variability. Provision of agricultural credit and access to off-farm employment are found to be highly effective policy entry points that deserve more empirical research.