Volcanogenic tsunamis are one of the deadliest volcanic phenomena. Understanding their triggering processes, and mitigating their effect, remains a major challenge. On 22 December 2018, flank failure of the Anak Krakatau volcano in Indonesia generated a tsunami that killed more than 400 people. This event was captured in unprecedented detail by high-resolution satellite imagery and eyewitness accounts. Here we combine historic observations with these recent data to—for the first time—interpret the internal architecture of Anak Krakatau, and reconstruct the failure, tsunamigenesis, and regrowth processes observed. We calculate the volume of material initially lost from the volcano flank failure and find that it was relatively small (∼0.1 km3) compared to the overall changes observed during the entire eruption, but it was nonetheless able to generate rapid tsunami waves with devastating impacts. The flank failure also changed the eruption style and the upper volcanic plumbing system, with the subsequent explosive eruptions destroying the summit and then partially rebuilding the lost flank. The nature of the flank failure was controlled by the internal structure of the island, and—although regrowth rate will be a primary control on flank failure intervals— the reconfiguring of the volcano’s internal vent network is likely to have re-stabilized it in the medium term. The findings demonstrate that hazard assessments at ocean islands must consider that even small flank failures, during unexceptional eruptions, can have catastrophic consequences.