Along with the blacktip reef shark (C. melanopterus) and the whitetip reef shark (Triaenodon obesus), the grey reef shark is one of the three most common sharks inhabiting Indo-Pacific reefs. They actively expel most other shark species from favored habitats, even species larger in size. In areas where this species co-exists with the blacktip reef shark, the latter species occupies the shallow flats, while the former stays in deeper water. Areas with a high abundance of grey reef sharks tend to contain few sandbar sharks (C. plumbeus), and vice versa; this may be due to their similar diets causing competitive exclusion.
Grey reef sharks feed mainly on bony fishes, with cephalopods such as squid and octopus being the second-most important food group, and crustaceans such as crabs and lobsters making up the remainder. The larger sharks take a greater proportion of cephalopods. These sharks hunt individually or in groups, and have been known to pin schools of fish against the outer walls of coral reefs for feeding. Hunting groups of up to 700 grey reef sharks have been observed at Fakarava atoll in French Polynesia. They excel at capturing fish swimming in the open, and they complement hunting whitetip reef sharks, which are more adept at capturing fish inside caves and crevices. Their sense of smell is extremely acute, being capable of detecting one part tuna extract in 10 billion parts of sea water. In the presence of a large quantity of food, grey reef sharks may be roused into a feeding frenzy; in one documented frenzy caused by an underwater explosion that killed several snappers, one of the sharks involved was attacked and consumed by the others.
Generally a coastal, shallow-water species, grey reef sharks are mostly found in depths of less than 60 m (200 ft). However, they have been known to dive to 1,000 m (3,300 ft). They are found over continental and insular shelves, preferring the leeward (away from the direction of the current) sides of coral reefs with clear water and rugged topography. They are frequently found near the drop-offs at the outer edges of the reef, particularly near reef channels with strong currents, and less commonly within lagoons. On occasion, this shark may venture several kilometers out into the open ocean.
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On the infrequent occasions when they swim in oceanic waters, grey reef sharks often associate with marine mammals or large pelagic fishes, such as sailfish (Istiophorus platypterus). There is an account of around 25 grey reef sharks following a large pod of bottlenose dolphins (Tursiops sp.), along with 25 silky sharks (C. falciformis) and a single silvertip shark. Rainbow runners (Elagatis bipinnulata) have been observed rubbing against grey reef sharks, using the sharks' rough skin to scrape off parasites.