Cassava (Manihot esculenta Crentz) is one of the most important root crops in tropical regions of the world. However, little or no study was carried out to determine the optimum rates of nitrogen (N) and potassium (K) for better cassava root yield. N and K fertilizers are the major factors limiting the growth and yield of cassava. Thus, this experiment evaluated the effect of N and K fertilizer rates on the growth, and yield of cassava. Four levels of N (0, 46, 92, and 138 kg N ha−1) and three levels of K (0, 60, and 120 kg K ha−1) were arranged in factorial combination in a randomized complete block design (RCBD) with three replications. The results revealed that the main effects of N fertilizer influenced all the studied parameters, while the main effect of K affected number of tubers per plant and tuber diameter. Interaction effect of N and K influenced fresh tuber yield of cassava. The highest fresh tuber yield of cassava was achieved from 92 kg N ha−1, whereas the lowest fresh tuber yield of cassava was obtained from the control plant. The economic analysis showed that higher net benefit and marginal rate of return were obtained from the application of 92 kg N ha−1, reflecting that it could be an optimum N for cassava yield in the study area.