Cassava brown streak viruses (CBSVs) are responsible for significant cassava yield losses in eastern sub-Saharan Africa. In the present work, we inoculated CBSV-susceptible and -resistant cassava varieties with a mixed infection of CBSVs using top-cleft grafting. Virus titres in grafted scions were monitored in a time course experiment in both varieties. We performed RNA-seq of the two cassava varieties at the earliest time-point of full infection in the susceptible scions. Genes encoding proteins in RNA silencing and salicylic acid pathways were regulated in the susceptible cassava variety but transcriptional changes were limited in the resistant variety. After infection, genes related to callose deposition at plasmodesmata were regulated and callose deposition was significantly reduced in the susceptible cassava variety. We also show that β-1,3-glucanase enzymatic activity is differentially regulated in the susceptible and resistant varieties. The differences in transcriptional responses to CBSV infection indicate that resistance involves callose deposition at plasmodesmata but does not trigger typical anti-viral defence responses. A meta-analysis of the current RNA-seq dataset and selected, previously reported, host-potyvirus and virus-cassava RNA-seq datasets revealed comparable host responses across pathosystems only at similar time points after infection or infection of a common host.