Reactive oxygen species (ROS), as signaling molecules, play a crucial role in the plant immune response. However, the mechanism(s) by which viruses affect ROS metabolism remain largely unexplored. Here, we found that wheat yellow mosaic virus (WYMV)-encoded P1 is a pathogenic protein. Transcriptomic and proteomic integrative analyses were performed on WYMV-infected overexpressing-P1 wheat and wild-type plants. A total of 9245 differentially expressed genes (DEGs) and 1383 differentially expressed proteins (DEPs) were identified in the transcriptome and proteome, respectively. At their intersection, 373 DEGs/Ps were identified. Enrichment analysis revealed that the expression of genes related to the ROS metabolism pathway in overexpressed P1 transgenic wheat (OE-P1) plants significantly increased during WYMV infection. We screened peroxidase (TaPOD) and thioredoxin reductase (TaTrxR) as they showed the most significant differences in expression. The silencing of TaPOD and TaTrxR revealed that they positively regulate WYMV infection by reducing ROS accumulation. Furthermore, hydrogen peroxide treatment induced WYMV resistance in wild-type wheat plants and OE-P1 transgenic plants. This study provides a theoretical basis for the role of P1 in plant viral infection.