Ending the hepatitis C virus (HCV) epidemic requires stopping transmission among networks of people who inject drugs (PWID). Identification of transmission networks through the application of genomic epidemiology may inform community response models that can quickly interrupt transmission. We retrospectively identified HCV RNA-positive specimens corresponding to 459 individuals tested in public health settings, including correctional facilities and syringe service programs, in Wisconsin from 2016-2017. Next-generation sequencing of HCV was conducted and analyzed for phylogenetic linkage using the CDC’s Global Hepatitis Outbreak Surveillance Technology platform. Transmission network analysis showed that 126 individuals were linked across 42 clusters (range: 2-11 individuals per cluster). Phylogenetic clustering was higher in rural communities and associated with female gender and younger age among rural residents. These data highlight that the increasing rurality of opioid injection use and HCV transmission among young PWID could be better supported by the expansion of molecular-based surveillance strategies to reduce transmission.Article Summary LineIntegrating existing public health surveillance and molecular analyses with Global Hepatitis Outbreak Surveillance Technology allows for the identification and characterization of growing HCV transmission clusters among key populations in Wisconsin.