Mosasaurs first appeared in the fossil record approximately 90 to 100 million years ago. This extinct marine reptile group was distantly related to the living Komodo dragon and other varanid lizards. It is believed that these large Late Cretaceous marine predators evolved from small semi-terrestrial lizards called aigialosaurs.

Tylosaurus was a dominant predator of the Western Interior Seaway. They would have dined on fish, sharks, smaller mosasaurs, plesiosaurs, and the flightless diving bird Hesperornis.