Effective management of reef corals requires knowledge of the extent to which populations are open or closed and the scales over which genetic exchange occurs, information which is commonly derived from population genetic data. Such data are sparse for Great Barrier Reef (GBR) corals and other organisms, with the studies that are available being mostly based on a small number of sampling locations spanning only part of the GBR. Using 11 microsatellite loci, we genotyped 947 colonies of the reef-building coral Acropora millepora from 20 sites spanning almost the full length of the GBR (∼12° of latitude and ∼1550 km). The results show a major divide between the southernmost central to southern offshore populations and all other sampled populations. We interpret this divide as a signature of allopatric divergence in northern and southern refugia during the Pleistocene glaciations, from which the GBR was subsequently recolonized. Superimposed on this pattern is a cross-shelf genetic division, as well as a separation of inshore populations south of the Cape Clifton Front at ∼21.5–22°S. Most inshore populations north of this, as well as mid-shelf populations in the northern and far northern GBR, are open, exchanging recruits frequently. In contrast, inshore populations south of the Cape Clifton Front and offshore populations in the central and southern GBR are largely self-seeding, at least within the spatial resolution that was achieved given our sampling intensity. Populations that have been impacted by recent disturbance events causing extensive coral mortality show no evidence of reduced genetic diversity.