Large scale cassava production is today being carried out season after season repeatedly on the same piece of land leading to decline in soil fertility and yield overtime. Research information to guide farmers on appropriate fertilizer management under such continuous cropping are few and poorly documented in south eastern Nigeria. A two-year field experiment was conducted during 2007 - 2009 at Uyo, a humid forest agro-ecology of south eastern Nigeria to assess the growth and yield response of cassava. Treatments included four rates each of nitrogen (N) and potassium(K) (0, 40, 80 and 120 kg/ha) in all possible factorial combination replicated thrice in a randomized complete block design. Application of N at the highest rate significantly (P = 0.05) increased plant height, produced higher number of leaves and branches/plant, stem girth, number and weight of tubers/plant and total fresh tuber yield compared with other treatments. The fresh tuber yield at 120 kg N/ha was however, comparable with that at 80 kg N/ha rate. Cassava growth, fresh tuber yield and all yield attributes peaked at 80 kg K/ha rate. The 120 kg N/ha and 80 kg K/ha rates increased fresh tuber weight by 48 and 45% and total fresh tuber yield by 36 and 27% respectively, compared with the control plots. The application of N between 80 and 120 kg/ha and K at 80 kg/ha appeared appropriate for optimum yield in our study area and are thus recommended.