Based on morphological similarities, Jack Garrick in 1982 grouped this species with the bignose shark (C. altimus) and the sandbar shark (C. plumbeus), while Leonard Compagno in 1988 placed it as the sister species of the grey reef shark (C. amblyrhynchos). A phylogenetic analysis based on allozyme data, published by Gavin Naylor in 1992, indicated that the Caribbean reef shark is the sister taxon to a clade formed by the Galapagos shark (C. galapagensis), dusky shark (C. obscurus), oceanic whitetip shark (C. longimanus), and the blue shark (Prionace glauca). However, more work is required to fully resolve the interrelationships within Carcharhinus.
Like many sharks, the Caribbean reef shark mainly eats bony fishes. The shark uses six keen senses to locate its prey: olfactory, visual, tactile (including water vibration sensitivity through a lateralis canal system), auditory, gustatory, and electric reception. The Caribbean reef shark is especially adapted to detecting low frequency sounds (indicative of a struggling fish nearby).
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In older literature, the scientific name of this species was often given as C. menisorrah. The blacktail reef shark (C. wheeleri), native to the western Indian Ocean, is now regarded as the same species as the grey reef shark by most authors. It was originally distinguished from the grey reef shark by a white tip on the first dorsal fin, a shorter snout, and one fewer upper tooth row on each side. Based on morphological characters, vertebral counts, and tooth shapes, Garrick (1982) concluded the grey reef shark is most closely related to the silvertip shark (C. albimarginatus). This interpretation was supported by a 1992 allozyme phylogenetic analysis by Lavery.
Grey reef sharks are active at all times of the day, with activity levels peaking at night. At Rangiroa, groups of around 30 sharks spend the day together in a small part of their collective home range, dispersing at night into shallower water to forage for food. Their home range is about 0.8 km2 (0.31 sq mi). At Enewetak in the Marshall Islands, grey reef sharks from different parts of the reef exhibit different social and ranging behaviors. Sharks on the outer ocean reefs tend to be nomadic, swimming long distances along the reef, while those around lagoon reefs and underwater pinnacles stay within defined daytime and night-time home ranges. Where there are strong tidal currents, grey reef sharks move against the water: towards the shore with the ebbing tide and back out to sea with the rising tide. This may allow them to better detect the scent of their prey, or afford them the cover of turbid water in which to hunt.