Arthropod-borne RNA viruses are a significant cause of human morbidity and mortality, but few vaccines and antiviral treatments are available. Therefore, a better understanding of host-pathogen interactions may aid in control efforts. RNA viruses have compact genomes which encode diverse RNA structures to regulate their life cycles. Some of these structures are recognized by cellular RNA binding proteins, including the DEAD-box (DDX) family of helicases, including the canonical RIG-I-like (RLR) sensors. Sensing of viral features by RLR helicases leads to the secretion of interferons (IFN) and the activation of antiviral effectors. However, viruses have evolved diverse strategies to evade and antagonize this canonical IFN-based defense pathway. Emerging evidence suggests that additional host RNA helicases operate outside of the canonical interferon pathway to restrict viral infection, but the full spectrum of antiviral DDXs and the structures they recognize remains unclear. Therefore, we sought to identify additional antiviral DDXs using siRNA screens and we characterized their function using CLIP-seq, mass spectroscopy, and biochemical assays. We found that DDX39A is antiviral against the chikungunya alphavirus as well as other medically relevant alphaviruses. We extended these studies and found that DDX39A is antiviral against other positive-sense RNA viruses but not negative-sense viruses. Upon infection, the predominantly nuclear DDX39A accumulates in the cytoplasm inhibiting alphavirus and flavivirus replication independent of the canonical interferon pathway. Biochemically, DDX39A strongly binds to alphavirus RNA and CLIP-seq studies showed that DDX39A interacts with a highly conserved alphavirus structure which is essential for the antiviral activity of DDX39A. Interestingly, infection with West Nile virus, a positive sense flavivirus led to post-translational modifications on DDX39A, which may impact its localization. CLIP-Seq analysis of transcripts bound by DDX39A during flavivirus infection revealed binding along the viral genome and enrichment of ER genes suggesting a distinct antiviral mechanism. Together, these studies identify novel antiviral factors that function in parallel with the canonical IFN-signaling pathway by recognizing specific viral RNA structures to restrict viral infections, revealing a new layer of cellular antiviral host defense.