Enteroviruses enter cells by receptor-mediated endocytosis. However, it is not fully understood how enteroviruses release their genomes and how enterovirus particles or RNA genomes cross the endosome membrane into the cytoplasm. We used cryo-electron microscopy to visualize enterovirus particles in the process of genome release. The exit of the RNA results in a loss of one, two, or three adjacent capsid-protein pentamers from a particle. The opening in the capsid, which is more than 120 Å in diameter, enables the release of the genome without the need to unwind its putative double-stranded RNA segments. We used cryo-electron tomography of infected cells to show that endosomes containing enteroviruses deform, rupture, and release virus particles into the cytoplasm. Blocking endosome acidification with bafilomycin A1 reduced the number of particles that released their genomes but did not prevent them from reaching the cytoplasm. Inhibiting post-endocytic membrane remodeling with wiskostatin promoted abortive enterovirus genome release in endosomes. Our results show that cellular membrane remodeling disrupts enterovirus-containing endosomes and thus releases the virus particles into the cytoplasm to initiate infection. The cells also contained empty capsids lacking pentamers of capsid proteins. Since the studied enteroviruses employ different receptors for cell entry but are delivered into the cytoplasm by cell-mediated endosome disruption, it is likely that most, if not all enteroviruses, and probably numerous other viruses from the family Picornaviridae, can utilize capsid opening and endosome rupture to infect cells.