Crop production in Sub-Saharan Africa is highly dependent on rainfall. We investigated the effects of water shortage and fertilizer on growth and storage root yields of cassava, which is increasingly grown as cash crop. Based on an integrated approach combining farm surveys, field experiments and crop growth modelling, we found that water shortage can reduce yields by 9-60%. However, application of potassium fertilizer increased cassava water use efficiency, radiation use efficiency and yield on potassium deficient soils. Thus better potassium management can protect cassava from drought and increase yields. Balanced nutrition that maximizes nitrogen, phosphorus and potassium use efficiencies substantially increased yields and produced up to twice the benefit:cost ratio of blanket fertilizer recommendations that ignored diversity in climate and soils. Our results indicate that site-specific fertilizer recommendations can be used to increase cassava yields under rain-fed conditions in West Africa, and fertilizers including potassium can be climate smart!