Infection of mammalian cells by vesicular stomatitis virus (VSV) triggers the activation of the innate immunity pathway. VSV RNA is recognized by RIG-I, leading to the activation of RIG-I and subsequent activation of the essential effector MAVS. To gain a comprehensive understanding of the molecular events occurring in VSV-infected THP1 cells, we employed data-independent acquisition (DIA) and diaPASEF techniques to profile the dynamic phosphoproteomes and proteomes of wild-type (WT), RIG-I knockout (KO), and MAVS KO THP1 cells. This approach enabled the quantification of approximately 8000 proteins and 11000 localized phosphopeptides. The in-depth proteomic and phosphoproteomic analyses provided insights into the molecular mechanisms underlying VSV-induced ATM-mediated PBX2 degradation. Moreover, the phosphoproteomic data revealed that VSV induces phosphorylation events in THP1 cells independently of RIG-I. Additionally, we identified five phosphosites on VSV-coding proteins and predicted the corresponding kinases in host cells. Overall, our findings offer a comprehensive proteomic and phosphoproteomic map of VSV stimulation, highlighting RIG-I or MAVS-related phosphorylation events. This resource serves as a valuable foundation for future studies aimed at understanding the RNA-sensing innate immunity signaling pathway.