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.
This species is taken by commercial and artisanal longline and gillnet fisheries throughout its range. It is valued for meat, leather, liver oil and fishmeal. The Caribbean reef shark is the most common shark landed in Colombia (accounting for 39% of the longline catch by occurrence), where it is utilized for its fins, oil and jaws (sold for ornamental purposes). In Belize, this species is mainly caught as bycatch on hook-and-line intended for groupers and snappers; the fins are sold to the lucrative Asian market and the meat sold in Belize, Mexico, and Guatemala to make "panades", a tortilla-like confection. A dedicated shark fishery operated in Belize from the mid-1900s to the early 1990s, until catches of all species saw dramatic declines. The flesh of this species may contain high levels of methylmercury and other heavy metals.
Ancient reefs buried within stratigraphic sections are of considerable interest to geologists because they provide paleo-environmental information about the location in Earth's history. In addition, reef structures within a sequence of sedimentary rocks provide a discontinuity which may serve as a trap or conduit for fossil fuels or mineralizing fluids to form petroleum or ore deposits.