Globally, sharks are under enormous pressure from fishing efforts. One such species is the silky shark, Carcharhinus falciformis, which occurs in all the Earth’s tropical oceans and is captured in large numbers in pelagic fisheries. Regionally, the silky shark is listed as Vulnerable to Near Threatened by the International Union for the Conservation of Nature due to high levels of direct and bycatch exploitation. Despite major conservation concerns about this species, little is known about its genetic status and level of demographic or evolutionary connectivity among its regional distributions. We report a genetic assessment of silky sharks sampled across a major portion of the species’ global range. We sequenced the complete mitochondrial DNA control region from 276 individuals taken from the western Atlantic and Indo-Pacific Oceans and the Red Sea. Overall, haplotype and nucleotide diversities were relatively large (0.93 ± 0.01 and 0.61 ± 0.32 %, respectively). Nucleotide diversity in Indo-Pacific sharks, however, was significantly lower and about half that in Atlantic sharks. Strong phylogeographic partitioning occurred between ocean basins. Furthermore, shallow but significant pairwise statistical differentiation occurred among most regional samples within the Indo-Pacific, but not the western Atlantic. Overall, at least five mitochondrial DNA populations of silky sharks were identified globally. Despite historically large population sizes, silky sharks appear to be isolated on relatively small spatial scales, at least in the Indo-Pacific, indicating that conservation and management efforts will need to be exerted at relatively small scales in a pelagic and highly vagile species.