Neutralising antibodies (NAb) play a key role in spontaneous clearance of hepatitis C virus (HCV) infection. NAbs with have been isolated and mapped to several domains on the envelope proteins, E1/E2. To date, however, the immunodominance of these epitopes in HCV infection remains unknown, hindering efforts to elicit epitope-specific responses by a vaccine. Furthermore, it remains unclear which epitope-specific response is associated with potent, broad neutralisation of HCV. The aim of the study was to identify immunodominant antibody epitopes that are associated with potent neutralisation, and spontaneous viral clearance. We analysed 145 time-matched samples from acute HCV infections with known clinical outcome. Polyclonal responses were mapped to the envelope proteins E1E2 using a panel of well-characterised antibodies covering unique E1E2 domains. Additionally, samples were analysed from a subjects that spontaneously cleared four infections over nearly ten years. Our analysis revealed that the majority of HCV-infected subjects target two immunodominant domains, termed Domains B and C. However, no epitopes were uniquely targeted by spontaneous clearers or those who developed chronic infections. We observed unique specificities in subjects infected with GT1 HCV when compared to those infected with GT3. Functional characterisation of patient plasma revealed that targeting AR3/Domain B is associated the potency of NAbs in early HCV infection. Repeated clearance of HCV in superlclearers, however, was associated with sustained NAbs targeting Domain C. Our results highlight regions within the HCV envelope that are highly immunogenic (AR3/Domain C) and those that are less immunogenic (AR5 and Domain E), and suggest that the specificity of the antibody response in clearers is similar to that in chronic progressors. Given that some of the most potent and broad NAbs appear to bind non-immunodominant epitopes, our results highlight the need for a strategy to design immunogens that illicit robust responses against such epitopes.