Juvenile Caribbean reef sharks are preyed upon by larger sharks such as the tiger shark (Galeocerdo cuvier) and the bull shark (C. leucas). Few parasites are known for this species; one is a dark variegated leech often seen trailing from its first dorsal fin.[4] Off northern Brazil, juveniles seek out cleaning stations occupied by yellownose gobies (Elacatinus randalli), which clean the sharks of parasites while they lie still on the bottom.[10] Horse-eye jacks (Caranx latus) and bar jacks (Carangoides ruber) routinely school around Caribbean reef sharks.[11]

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.[3] 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.[4] 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.[11]

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.[20] 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.[14] Hunting groups of up to 700 grey reef sharks have been observed at Fakarava atoll in French Polynesia.[21][22] 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.[4] Their sense of smell is extremely acute, being capable of detecting one part tuna extract in 10 billion parts of sea water.[13] 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.[23]

Corals, including some major extinct groups Rugosa and Tabulata, have been important reef builders through much of the Phanerozoic since the Ordovician Period. However, other organism groups, such as calcifying algae, especially members of the red algae Rhodophyta, and molluscs (especially the rudist bivalves during the Cretaceous Period) have created massive structures at various times. During the Cambrian Period, the conical or tubular skeletons of Archaeocyatha, an extinct group of uncertain affinities (possibly sponges), built reefs. Other groups, such as the Bryozoa have been important interstitial organisms, living between the framework builders. The corals which build reefs today, the Scleractinia, arose after the Permian–Triassic extinction event that wiped out the earlier rugose corals (as well as many other groups), and became increasingly important reef builders throughout the Mesozoic Era. They may have arisen from a rugose coral ancestor. Rugose corals built their skeletons of calcite and have a different symmetry from that of the scleractinian corals, whose skeletons are aragonite. However, there are some unusual examples of well-preserved aragonitic rugose corals in the late Permian. In addition, calcite has been reported in the initial post-larval calcification in a few scleractinian corals. Nevertheless, scleractinian corals (which arose in the middle Triassic) may have arisen from a non-calcifying ancestor independent of the rugosan corals (which disappeared in the late Permian).