Cassava brown streak disease (CBSD) is a major constraint to cassava production in Uganda. The disease is caused by two ipomovirus species: Cassava brown streak virus (CBSV) and Ugandan cassava brown streak virus (UCBSV), both transmitted by the whitefly vector (Bemisia tabaci). Since the outbreak of the CBSD epidemic in Uganda in 2004, knowledge of its spread in the field is still limited. In this study, five cassava genotypes with varying levels of resistance to CBSD: TME 204 (susceptible), I92/0067, MH 97/2961, MH 96/0686 (moderately tolerant) and NASE 3 (tolerant) were used to evaluate the effect of genotype and prevailing disease pressure on CBSD spread in Uganda. The experiment was established in a randomised Complete Block Design (RCBD) in three sites of varying CBSD disease pressure: high (Wakiso), moderate (Kamuli) and low (Lira) in November, 2009 to November, 2010. Disease incidences (%), apparent infection rate (r), area under disease progress curves (AUDPC) were determined and population of the whitefly vector monitored monthly for 8 months. Genotype and disease pressure significantly affected CBSD incidence (P = .001), with Lira recording no noticeable disease spread even in the susceptible genotype TME 204. On the contrary, in Wakiso and Kamuli final disease incidence was maximum (100%) in the genotypes I92/0067, TME 204 and MH 97/2961 while the tolerant genotype NASE 3 had low final disease incidence of ≤ 5%. Mean whitefly population varied with site (P = .001) and there was a positive interaction between whitefly population and disease pressure hence the rapid CBSD spread in Kamuli and Wakiso. There was a high correlation (r = .994) between foliar and root CBSD incidence hence high CBSD root incidence in Kamuli and Wakiso. From these results, it is evident that high disease pressure, use of susceptible genotypes and high whitefly population significantly enhanced CBSD spread and development.