Archaeological records documenting the timing and use of northern Great Barrier Reef offshore islands by Aboriginal and Torres Strait Islander peoples throughout the Holocene are limited when compared to the central and southern extents of the region. Excavations on Lizard Island, located 33 km from Cape Flattery on the mainland, provide high resolution evidence for periodic, yet sustained offshore island use over the past 4000 years, with focused exploitation of diverse marine resources and manufacture of quartz artefacts. An increase in island use occurs from around 2250 years ago, at a time when a hiatus or reduction in offshore island occupation has been documented for other Great Barrier Reef islands, but concurrent with demographic expansion across Torres Strait to the north. Archaeological evidence from Lizard Island provides a previously undocumented occupation pattern associated with Great Barrier Reef Late Holocene island use. We suggest this trajectory of Lizard Island occupation was underwritten by its place within the Coral Sea Cultural Interaction Sphere, which may highlight its significance both locally and regionally across this vast seascape.