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.
Despite sharks being portrayed as notorious aggressive animals, very few incidents have involved blacktip reef sharks, none being fatal. Still the importance of an apex predator is vital to a balanced and healthy ecosystem. Unfortunately, this species is very susceptible to reef gill netting. And sharks all around continue to be threatened by fishing pressure resulting in a decrease in many shark populations.
During mating, the male grey reef shark will bite at the female's body or fins to hold onto her for copulation. Like other requiem sharks, it is viviparous: once the developing embryos exhaust their supply of yolk, the yolk sac develops into a placental connection that sustains them to term. Each female has a single functional ovary (on the right side) and two functional uteruses. One to four pups (six in Hawaii) are born every other year; the number of young increases with female size. Estimates of the gestation period range from 9 to 14 months. Parturition is thought to take place from July to August in the Southern Hemisphere and from March to July in the Northern Hemisphere. However, females with "full-term embryos" have also been reported in the fall off Enewetak. The newborns measure 45–60 cm (18–24 in) long. Sexual maturation occurs at around seven years of age, when the males are 1.3–1.5 m (4.3–4.9 ft) long and females are 1.2–1.4 m (3.9–4.6 ft) long. Females on the Great Barrier Reef mature at 11 years of age, later than at other locations, and at a slightly larger size. The lifespan is at least 25 years.
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.
There is a variety of biotic reef types, including oyster reefs and sponge reefs, but the most massive and widely distributed are tropical coral reefs. Although corals are major contributors to the framework and bulk material comprising a coral reef; the organisms most responsible for reef growth against the constant assault from ocean waves are calcareous algae, especially, although not entirely, coralline algae.