What is already known about this topic? Targeted testing for hepatitis C virus (HCV) infection in emergency departments (EDs) has been demonstrated to be a high-yield and effective intervention for identifying previously unrecognized infections, especially among persons born during 1945–1965. What is added by this report? Opt-out, universal HCV screening in EDs identified that nearly half (47.5%) of infections were among persons born after 1965. What are the implications for public health practice? Opt-out, universal screening in EDs can identify a larger number of previously unrecognized HCV infections, especially among persons born after 1965. ED-based opt-out, universal hepatitis C screening can be vital in combating and surveilling the interrelated epidemics of opioid overdose and bloodborne viral infections through harm-reduction interventions and navigation to HCV treatment.