Abstract: As the price of chemical fertilizers in the Nigerian market continues to go high thereby making chemical fertilizers unreachable to peasant farmers and the urgent need to improve the fertility of the soils in which sweet potato (Ipomoea batatas) is grown, this investigation was carried out at Umudike, Southeastern Nigeria, to evaluate the comparative effect of Cow Dung (CD) and chemical fertilizer on soil properties, nutrient uptake and yield of sweet potato. The experiment was laid out in a randomized complete block design, with four replications. The treatments consisted of 4 t ha-1 CD, 400 t ha-1 NPK (15:15:15) fertilizer, 2 t ha-1 CD+200 kg ha-1 NPK fertilizer, 1 t ha-1 CD+300 kg ha-1 NPK fertilizer, 3 t ha-1 CD+100 kg ha-1 NPK fertilizer and control which did not receive any treatment. The result of the investigation showed that application of 3 t ha-1 CD+100 kg ha-1 NPK fertilizer improved Soil Organic Matter (SOM), available phosphorus, exchangeable cations, Effective Cation Exchange Capacity (ECEC) and base saturation more than other treatments. The treatments significantly (p = 0.05) improved nutrient uptake when compared to the control, but application of 3 t ha-1 CD+100 kg ha-1 NPK fertilizer recorded the highest values. The treatments improved the growth and yields of sweet potato more than the control with the highest tuber yield (8.9 t ha-1) being produced with application of 3 t ha-1 CD + 100 kg ha-1 NPK fertilizer. Application of 3 t ha-1 CD+100 kg ha-1 NPK fertilizer is hereby recommended to farmers improvement of soil fertility and growth of sweet potato in this part of Nigeria.