Soybean mosaic virus (SMV) is a worldwide disease of soybean (Glycine max (L.) Merr.) that can cause serious reduction in yield and seed quality. Soybean cv. Qihuang-1 is an important source of resistance to SMV in China, carrying a resistance gene (R_SC3Q) against SMV strain SC3. In order to discover genes and networks regulated by R_SC3Q-mediated resistance in Qihuang-1, we analysed transcriptome data of a pair of near-isogenic lines, R (R_SC3Q) and S (r_SC3Q), from the cross Qihuang-1 × Nannong 1138-2 (r_SC3Q), after SC3 inoculation. Many differentially expressed genes (DEGs) were identified in the R and S lines at 6, 20 and 48 h post-inoculation. Based on pathway-enrichment analysis of DEGs, three genes encoding calmodulin-like protein (Glyma03g28650, Glyma19g31395 and Glyma11g33790) with downregulated expression in the S line were identified in the plant–pathogen interaction pathway at 6 h post-inoculation. Analyses by quantitative real-time PCR were performed to verify that these three genes were not beneficial for SMV infection. Our results also revealed a complex plant-hormone signal network in R_SC3Q-mediated resistance during the early stage of SMV infection. Expression of jasmonic acid repressor genes (TIFY/JAZ) and abscisic acid-induced genes (PP2C3a) was upregulated in the R line but not the S line. More DEGs related to indole-3-acetic acid were found in the R line than the S line, and no salicylic acid-related DEGs were identified. These results suggest that suppression of jasmonic acid or promotion of abscisic acid is important for R_SC3Q-mediated resistance against SC3, and that salicylic acid may not act as a main regulator of R_SC3Q-mediated resistance during early stages of SC3 infection. Growth and development were greatly affected through R_SC3Q-mediated resistance responses after SC3 infection. Our understanding would be enhanced by identification of factors associated with R_SC3Q that help to trigger the resistance response.