Coral reefs provide essential goods and services but are degrading at an alarming rate due to local and global anthropogenic stressors. The main limitation that prevents the implementation of adequate conservation measures is that connectivity and genetic structure of populations are poorly known. Here, the genetic diversity and connectivity of the brooding scleractinian coral Seriatopora hystrix were assessed at two scales by genotyping ten microsatellite markers for 356 individual colonies. S. hystrix showed high differentiation, both at large scale between the Red Sea and the Western Indian Ocean (WIO), and at smaller scale along the coast of East Africa. As such high levels of differentiation might indicate the presence of more than one species, a haploweb analysis was conducted with the nuclear marker ITS2, confirming that the Red Sea populations are genetically distinct from the WIO ones. Based on microsatellite analyses three groups could be distinguished within the WIO: (1) northern Madagascar, (2) south-west Madagascar together with one site in northern Mozambique (Nacala) and (3) all other sites in northern Mozambique, Tanzania and Kenya. These patterns of restricted connectivity could be explained by the short pelagic larval duration of S. hystrix, and/or by oceanographic factors, such as eddies in the Mozambique Channel (causing larval retention in northern Madagascar but facilitating dispersal from northern Mozambique towards south-west Madagascar). This study provides an additional line of evidence supporting the conservation priority status of the Northern Mozambique Channel and should inform coral reef management decisions in the region.