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.
This species is commonly found in shallow waters on and near coral reefs and occasionally in brackish waters. Juveniles are typically found in extremely shallow water (±15 to 100 cm) inside lagoons, often swimming along the shoreline; adults typically occur on shallow parts of the forereef, often moving over the reef crest and onto the reef flat at flood tide. Individual adults inhabit a relatively small home range of ±2.5 km2 and appear to reside close to their home reef but occasionally cross deepwater channels between adjacent reefs.
Off Enewetak, grey reef sharks exhibit different social behaviors on different parts of the reef. Sharks tend to be solitary on shallower reefs and pinnacles. Near reef drop-offs, loose aggregations of five to 20 sharks form in the morning and grow in number throughout the day before dispersing at night. In level areas, sharks form polarized schools (all swimming in the same direction) of around 30 individuals near the sea bottom, arranging themselves parallel to each other or slowly swimming in circles. Most individuals within polarized schools are females, and the formation of these schools has been theorized to relate to mating or pupping.
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.