[3] This species dwells on sand, weed, and mud flats from the low intertidal to shallow subtidal zones,[3] in 20 foot (6 m) deep water.

They are found at depths ranging from 0 to 100 m.[8] Triplofusus giganteus is a predator, with a diet that consists primarily of large gastropods,[9] such as tulip shell (Fasciolaria tulipa), the lightning whelk (Sinistrofulgur perversum), and the queen conch (Lobatus gigas) as well as some Murex species.

[10][11] T. giganteus rarely eats bivalves, even when they are readily available, with the exception of pen shells in the genus Atrina, which can comprise 20% of its diet.

[9] It has been observed (in an aquarium setting) to eat small hermit crabs of the species Clibanarius vittatus.

[citation needed] Cannibalism has been documented in captive T. giganteus, but only seems to occur in individuals that have been deprived of sufficient food.

In classic Mayan art, the Horse Conch is shown being utilised in many ways including as paint and ink holders for elite scribes, and also as a bugle or trumpet.

In southern Florida, Native Americans, including the Calusa and Tequesta, used the horse conch to make several types of artifact.