Sweet potato is a vegetatively propagated crop where vine cuttings from previous crops or volunteer plants are used as planting material. This practice can lead to the accumulation of systemic pathogens, especially viruses. However, the contribution of this practice to degeneration of sweet potato cultivars in Uganda has been only speculative, hence the need to document the rate of cultivar degeneration in high and low sweet potato virus disease pressure zones. Four cultivars of sweet potato – ‘Beauregard’, ‘Dimbuka’, ‘Ejumula’ and ‘NASPOT 1’ – were planted in a series of field trials in central (Kabanyolo) and Eastern (Serere) Uganda over five generations (G1, G2, G3, G4 and G5). The trials started with virus-free planting material and each succeeding trial retained planting material from the previous one, as well as receiving fresh clean material. Data were recorded on virus incidence and severity monthly for 4 months, root yield and vine weight at harvest after 6 months. Virus symptoms were observed 1 month after planting in all the plant generations, with Sweet potato feathery virus and Sweet potato chlorotic stunt virus being the most prevalent viruses detected. The cultivars ‘Beauregard’ and ‘Ejumula’ had highest disease incidence and severity, with the latter collapsing after a single season in both locations. Storage root yields and numbers were greatest in G1 but remained similar although less in all subsequent generations (G2, G3, G4 and G5) for each cultivar. Since it is impractical to provide fresh planting material each year for farmers, the focus should be on breeding more resistant varieties of sweet potato.