Rapid detection and appropriate response to pathogen are essential for host defense against infectious disease. Innate immune responses depend upon the recognition of pathogen- or danger-associated molecular patterns (PAMPs or DAMPs) by pattern recognition receptors to initiate intracellular signaling pathways that culminate in the expression of host defense molecules such as IFN and/or pro-inflammatory cytokines like interleukin-1β (IL-1β). IL-1β, a product of inflammasome activation, is a potent inducer of nuclear factor κB (NF-κB)-responsive genes. While it has been observed that IL-1 receptor (IL-1R) signaling also induces the activation of the inhibitor of NF-κB kinase (IKK)-related kinase, TANK-binding kinase 1 (TBK1), a functional role for this kinase in IL-1R signaling has not been elucidated. Furthermore, it has been published that despite its ability to activate TBK1, the essential kinase for IRF3 activation and downstream IFN induction, IL-1β does not activate IRF3 in mouse embryonic fibroblasts. Here we report that exogenous IL-1β does indeed induce IRF3 activation and IRF3-dependent innate immune response genes in mouse myeloid cells, human myeloid, epithelial and endothelial cells. In our studies, IL-1β-induced IRF3 activation is independent of cell death and is dependent upon the essential DNA sensing pathway adaptor, stimulator of interferon genes (STING). We also demonstrate that exogenous IL-1β augments PAMP-induced IFN production and STAT signaling. Additionally, we show that IL-1R is required for maximal IRF3-mediated IFN production and immune activation in response to various PAMPs and RNA viruses. These studies identify a new role for IL-1R signaling in the onset and/or enhancement of the antiviral actions of IFN and IFN-stimulated genes, with exciting new implications for the role of STING in integrating antiviral and inflammatory cues for host defense.