Rice stripe virus (RSV) has become a major pathogen of rice. To determine how the rice transcriptome is modified in response to RSV infection, we used RNA-Seq to perform a genome-wide gene expression analysis of a susceptible rice cultivar. The transcriptomes of RSV-infected samples were compared to those of mock-treated samples at 3, 7, and 15 days post-infection (dpi). From 8 to 11% of the genes were differentially expressed (>2-fold difference in expression) in RSV-infected vs. noninfected rice. Among them, 532 genes were differentially expressed at all three time points. Surprisingly, 37.6% of the 532 genes are related to transposons. Gene ontology enrichment analysis revealed that many chloroplast genes were down-regulated in infected plants at 3 and 15 dpi. Expression of genes associated with cell differentiation and flowering was significantly down-regulated in infected plants at 15 dpi. In contrast, most of the up-regulated genes in infected plants concern the cell wall, plasma membrane, and vacuole and are known to function in various metabolic pathways and stress responses. In addition, transcripts of diverse transcription factors gradually accumulated in infected plants with increasing infection time. We also confirmed that the expression of gene subsets (including NBS-LRR domain-containing genes, receptor-like kinase genes, and genes involving RNA silencing) was changed by RSV infection. Taken together, we demonstrated that down-regulation of genes related to photosynthesis and flowering was strongly associated with disease symptoms caused by RSV and that up-regulation of genes involved in metabolic pathways, stress responses, and transcription was related to host defense mechanisms.