[11] Greater sirens are carnivorous and prey upon invertebrates (such as insects, crustaceans, gastropods, bivalves, spiders, molluscs, and crayfish)[11] and aquatic vertebrates (such as small fish)[11] with a possible preference for molluscs (such as snails and freshwater clams),[8][12] although they have been observed to eat vegetation such as algae.

[14] The oral morphology of the greater siren contribute little to the mastication of food and does not rupture or grind ingested invertebrates, algae, or plants requiring prior fermentation in the gut.

Greater sirens can vocalize, producing clicks or yelps sounding similar to the call of the American green tree frog.

This has been seen during times of drought and hydroperiod fluctuations[18] and might last as long as three years in large individuals with high lipid content.

[2] A population of sirens in the Rio Grande around Texas and Tamaulipas in Mexico was tentatively determined to be S. lacertina; however, recent studies have refuted this claim.

Greater sirens live in wetlands, preferring those with a slow or nonexistent current and a thick layer of organic material.

[22] Associated habitat for greater sirens includes vegetative ditches, and various other forms of slow, or stagnant bodies of water.

The use of aquatic funnel traps, commercially produced to capture crayfish, has been found effective for use on Siren and Amphiuma species and there is no risk of drowning the animals.

[24] Greater sirens are classified as Least Concern by the International Union for Conservation of Nature, although they have been extirpated from some of their former range due to habitat loss.