The study assessed the effect of Cattle manure and NPK fertilizer on the growth and yield of potatoes. The study was guided by two objectives. To compare the effect of cattle manure and NPK on vegetative growth of potato plants, to compare the effect of cattle manure and NPK fertilizer on tuber yield of potatoes. The study used a Randomized Complete Block Design (RCBD), with two treatments and a control experiment replicated three times. The field was divided into three, each with three plots measuring 2.7m by 2.7m. Cattle manure gave the most height compared to NPK fertilizer and the control. There were more shoots formed on plants that were fertilized using cattle manure followed by NPK and lastly control. Cattle manure produced the largest size compared to NPK fertilizer and control experiment. Cattle Manure also produced the most marketable tuber weight compared to NPK in the control experiment. The study recommends using cattle Manure for potato production in Uganda as it was found to increase crop performance and subsequent yield, which is beneficial to the environment and safe for farmers.