Aquaculture of Pacific oysters (Crassostrea gigas) around the world is stymied by mortality events triggered by Ostreid herpesvirus 1 (OsHV-1). In Tomales Bay, California, where OsHV-1 is endemic, breeding through family-based pedigree selection has achieved considerable genetic gains in survival to mortality events. In this study, a genome-wide association study with unselected and selected oyster families was performed that led to the detection of one quantitative trait locus (QTL) on chromosome 8 of the Pacific oyster genome that was associated with survival to mortality events in Tomales Bay and explained 13% of the phenotypic variance. RT-qPCR was used to determine that the basal upregulation of two antiviral genes, IRF2 and Viperin, was also associated with this QTL. Marker-assisted selection for this QTL was performed and families selected in this manner had 47% greater survival breeding values than families selected using pedigree selection alone. Future fine-mapping of this QTL could potentially provide a mechanistic understanding of OsHV-1 tolerance in Tomales Bay.