The necessity for pathogen recognition of viral infection by the innate immune system in initiating early innate and adaptive host defenses is well documented. However, little is known about the role these receptors play in the maintenance of adaptive immune responses and their contribution to resolution of persistent viral infections. Here, we demonstrate a non-redundant functional requirement for both nucleic acid-sensing Toll-like receptors (TLR) and RIG-I-like receptors (RLR) in the control of a mouse model of chronic viral infection. Whereas the RLR pathway was important for production of type I interferons and optimal CD8+ T cell responses, nucleic acid-sensing TLRs were largely dispensable. In contrast, optimal anti-viral antibody responses required intact signaling through nucleic acid-sensing TLRs, and the absence of this pathway correlated with less virus-specific antibody and deficient long-term virus control of a chronic infection. Surprisingly, absence of the TLR pathway had only modest effects on antibody production in an acute infection with a closely related virus strain, suggesting that persistent TLR stimulation may be necessary for optimal antibody responses in a chronic infection. These results indicate that innate virus recognition pathways may play critical roles in the outcome of chronic viral infections through distinct mechanisms.