African whitefly Bemisia tabaci is a yield-limiting pest of the subsistence crop cassava through feeding and vectoring viral diseases. To address this issue, the African Cassava Whitefly Project is identifying whitefly resistance in South American cassava for selective breeding into African cassava. The collaborative efforts of project members at the International Center for Tropical Agriculture, UCR and the Royal Holloway University of London have focused on the genetic, transcriptomic and metabolic basis of resistance to Latin American whitefly Aleurotrachelus socialis in whitefly-resistant Ecuadorian cassava genotype ECU72. Here, the whitefly- and defense-hormone-responsive transcriptomes of ECU72 and its susceptible counterpart COL2246 have been defined for analysis and integration with these data sets. To characterize the cassava-whitefly interaction, we identified a core transcriptome response of Pathogenesis-related (PR) gene families to whitefly infestation in four whitefly-susceptible genotypes. Defense-hormone responses of COL2246 revealed that whitefly-responsive PR genes were mainly co-regulated by salicylic acid (SA) and jasmonic acid (JA). Cell-wall-related PR gene families were dominant in the responses to whiteflies and biotic stressors. PR gene phylogenies and biotic-stress-responsive transcriptomes revealed a possible selection in cassava for expansion of certain PR genes responsive to whiteflies and microbes. More global characterization of the cassava-whitefly interaction compared whitefly-, SA-, JA-, ethylene-, and abscisic acid (ABA)-responsive transcriptomes in ECU72 and COL2246. SA responses were faster and more prolonged in ECU72, and SA-responsive genes showed reciprocity between genotypes, suggesting importance of crosstalk regulators. Hormone responses during infestation revealed evidence of ABA-mediated resistance in ECU72 and SA-mediated susceptibility in COL2246. Comparisons between cassava and Arabidopsis revealed divergent transcriptome responses to SA and JA. Enrichment analyses of whitefly- and hormone-regulated genes showed that early infestation prompted cell-wall-based defenses in ECU72, while late infestation invoked SA-signaling and immunity defenses in COL2246. To identify whitefly defense genes, eQTL analysis was performed utilizing F1 progeny generated from crosses of ECU72 with whitefly-susceptible COL2246 or 60444. Criteria applied to eQTLs identified immunity, defense-signaling and cell-wall-related processes as possibly important in defense against whiteflies. eQTL-identified genes involved in ABA responses, monolignol biosynthesis, and chitin perception/response are proposed as possible whitefly resistance factors for evaluation in transgenic cassava.