Wheat (Triticum aestivum L.) cultivation has been globally restricted by many plant viruses such as the Wheat streak mosaic virus (WSMV), Barley stripe mosaic virus (BSMV), and Brome mosaic virus (BMV). Herein, the transcriptome of wheat was in silico analyzed under mono- (WSMV, BSMV, or BMV), bi- (BMV&BSMV, BMV&WSMV, and BSMV&WSMV), and tripartite (WSMV, BSMV, and BMV) infections using the RNA-seq technique. Total numbers of 1616/270, 5243/690 and 5589/2183 differentially expressed genes (DEGs) were up/down-regulated during the bipartite infection of BMV&BSMV, BMV&WSMV and BSMV&WSMV, respectively, while the tripartite infection resulted in the up/down-regulation of 6110/2424 DEGs. The NAC and bHLH were the most commonly presented transcription factor (TF) families in WSMV, BMV, and BSMV infection, while C2H2, bHLH, and NAC were the TF families involved in BMV&WSMV, BMV&BSMV, and BSMV&WSMV infections, respectively. The RLK-Pelle_DLSV was the most commonly expressed protein kinase (PK) family in all infection patterns. Promoter analysis showed that the motifs involved in gene expression, CUL4 RING ubiquitin ligase complex, stress response, brassinosteroid response, and energy-related pathways were significantly induced in wheat plants under bipartite infections. The gene expression network analysis showed that a defense-related gene, i.e., allene oxide synthase (AOS) gene, serves as a crucial hub in tripartite infections.