Echovirus 30 (E30), a serotype of Enterovirus B (EV-B), recently emerged as a major causative agent of aseptic meningitis worldwide . E30 is particularly devastating in the neonatal population and currently no vaccine or antiviral therapy is available . Here we characterize two highly potent E30-specific monoclonal antibodies , 6C5 and 4B10, which efficiently block binding of the virus to its attachment receptor CD55 and uncoating receptor FcRn . Combinations of 6C5 and 4B10 augment the sum of their individual anti-viral activities . High-resolution structures of E30-6C5-Fab and E30-4B10-Fab define the location and nature of epitopes targeted by the antibodies . 6C5 and 4B10 engage the capsid loci at the north rim of the canyon and in-canyon, respectively . Notably, these regions exhibit antigenic variability across EV-Bs, highlighting challenges in development of broad-spectrum antibodies . Our structures of these neutralizing antibodies of E30 are instructive for development of vaccines and therapeutics against EV-B infections.