Mercenaria mercenaria is a protandric hermaphrodite, with smaller individuals being male and transforming into females as they increase in size. Larval development is planktotrophic, with veliger larvae, initially 170-240 μm in diameter, settling after about 12 days. The early juvenile is byssate, with relatively longer siphons and a thinner, more heavily sculptured shell. Growth rate varies greatly according to environmental conditions; growth to marketable length (48 mm or littlenecks) requires 15 months in warm southern waters but four years in cooler northern waters. Shell layers in cross section show that growth occurs constantly through warm periods, punctuated by growth stoppages in winter. Very large specimens (ca. 15 cm or chowder clams) have been estimated to be at least 40 years old.
Mercenaria mercenaria inhabits intertidal to shallow subtidal mud, sandy or seagrass habitats. It is a relatively rapid burrower, and its adult size and shell thickness aid in deterring most fish and crustacean predators. It is tolerant of a wide range of salinity and water temperature, but requires oceanic conditions for spawning.