Fonio millet (Digitaria exilis), a small-grained cereal, plays an important role in food security in West Africa. As part of efforts to increase its productivity, we studied the effects of moderate levels of nitrogen (0, 15.0 and 30.0 kg N ha−1), phosphorus (0, 6.6 and 13.2 kg P ha−1) and potash (0, 12.5 and 25.0 kg K ha−1) fertilizers under varying climatic conditions. The three experimental sites at Bareng and Bordo in Guinea, and Cinzana in Mali, are representative of the distribution of fonio millet in West Africa. The average recorded grain yields were 1.51 ± 0.229, 1.08 ± 0.141 and 0.47 ± 0.182 t ha−1 in Bareng, Bordo and Cinzana, respectively. We observed a marginal to significant impact of N fertilization coupled, in Bordo, with a significant interaction with the P and K response. This interaction was highlighted by the limited effect of N without P or K fertilization or with the application of only one of these two major elements. Overall, N application as low as 15 kg ha−1 led to a 12–22% increase in production if the P and K applications were not limited. For better control over the risks associated with poor soil fertility and limited rainfall, it appeared to be more effective to apply moderate levels of N, P and K fertilizers to the fonio millet crop than a large amount of one of these nutrients.