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.
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.
The Caribbean reef shark infrequently attacks humans. In general, a shark attack on a human is behaviorally similar to an attack upon natural prey. A human is more susceptible to being attacked if the shark is cornered and feels that there is no escape route. In situations like these, the shark may rake the victim during the attack resulting in lacerations.
Despite its abundance in certain areas, the Caribbean reef shark is one of the least-studied large requiem sharks. They are believed to play a major role in shaping Caribbean reef communities. These sharks are more active at night, with no evidence of seasonal changes in activity or migration. Juveniles tend to remain in a localized area throughout the year, while adults range over a wider area.
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).