The geologically abrupt appearance in the fossil record of almost all animal phyla is referred to as the Cambrian radiation or “explosion” of life on Earth. Also known as “Darwin’s dilemma,” because it seemingly posed a major problem for his theory of gradual evolution, it coincided with the initiation of the first of the two principal global marine transgressions of the Phanerozoic. Although now seen as more protracted, it is still one of the most striking and critical events in the history of the biosphere. Almost all paleogeographic reconstructions for the early Cambrian feature a previously isolated Laurentia, the core of ancestral North America. Yet geological evidence from five continents, integrated here for the first time, indicates that the present-day “southern cone” of Laurentia was still attached to the newly amalgamated supercontinent of Gondwanaland into Cambrian times. Laurentia was then isolated by the development of a major deep oceanic connection between the opening Iapetus Ocean basin and the already well-developed paleo-Pacific. As the marine transgression advanced, major changes in ocean chemistry occurred, upwelling generated phosphorite deposits, and the number of fossilized metazoan phyla “exploded” with morphologic disparity between Laurentia and Gondwanaland already established. The development of this deep oceanic gateway, and of an ocean floor–consuming and arc-generating subduction zone along virtually the entire margin of Gondwanaland shortly thereafter, need to be taken into account in consideration of the global environmental and biotic changes associated with the Neoproterozoic-Phanerozoic transition.