The Cretaceous-Paleogene (K-Pg) boundary is marked by a major mass extinction, yet this event is thought to have had little effect on the diversity of lizards and snakes (Squamata). A revision of fossil squamates from the Maastrichtian and Paleocene of North America shows that lizards and snakes suffered a devastating mass extinction coinciding with the Chicxulub asteroid impact. Species-level extinction was 83%, and the K-Pg event resulted in the elimination of many lizard groups and a dramatic decrease in morphological disparity. Survival was associated with small body size and perhaps large geographic range. The recovery was prolonged; diversity did not approach Cretaceous levels until 10 My after the extinction, and resulted in a dramatic change in faunal composition. The squamate fossil record shows that the end-Cretaceous mass extinction was far more severe than previously believed, and underscores the role played by mass extinctions in driving diversification.