Male mussels release sperm into the water column, where females draw it in through their siphons during feeding and respiration. Mussel density and water flow conditions influence fertilization success. Females retain eggs in their gills until they develop into mature larvae called glochidia.

The modified larvae, called glochidia, begin maturation in the gills of females until they reach an obligate ectoparasitic stage that requires a fish host. Like other members of the genus Quadrula, female rabbitsfoot use all four gills as a brooding pouch, called the marsupium, for the glochidia. The rabbitsfoot is tachytictic, meaning a short-term brooder, with females brooding between May and late August in the Spring, Black, and Little rivers in Arkansas, Kansas and Missouri.

Female rabbitsfoot release glochidia within conglutinates, which are defined as aggregates of eggs, formed as molds in the water tubes of the marsupial demibranch of the female. The females typically retain glochida and fragmentary conglutinates in their mantle and attract sight-feeding minnows by using it as a visual lure. When a fish host approaches or touches the excurrent aperture, the female reflexively release small quantities of conglutinate fragments and free glochidia from it into the water column. The glochidia attach and encyst on the gills of suitable fish hosts that provide nourishment to glochidia to continue growing. When metamorphosis is complete, the juvenile mussels excyst, meaning emerge, from the fish host and drop onto the stream floor. If habitat is favorable, juveniles develop into adults.

In 2000, M.C. Barnhart and M.S. Baird collected glochidia of the rabbitsfoot from the Black River, Arkansas and tested five species of fish as potential hosts. They observed transformation of glochidia on blacktail shiner (Cyprinella venusta), but not on fathead minnow (Pimephales promelas), mimic shiner (Notropis volucellus), emerald shiner (Notropis atherinoides) or bluegill (Lepomis macrochirus). In 2007, T.B. Fobian compared potential fish hosts for populations of the rabbitsfoot from the Spring, Black and Little rivers in Arkansas, Kansas and Missouri and found that blacktail shiner, red shiner (Cyprinella lutrensis), bluntface shiner (Cyprinella camura), spotfin shiner (Cyprinella spiloptera) and cardinal shiner (Luxilus cardinalis) were suitable hosts for glochidia of all three populations of the rabbitsfoot. Rosyface shiner (Notropis rubellus), striped shiner (Luxilus chrysocephalus) and emerald shiner (Notropis. atherinoides) also served as hosts for glochidia, but not in all populations tested, as documented by T.B. Fobian in 2007. More recently, host fish trials have identified scarlet shiner (Lythrurus fasciolaris) and striped shiner as a suitable hosts for glochidia collected from females in the Paint Rock River, Alabama.

Suitable habitat for the rabbitsfoot occurs in small to medium-sized streams and some larger rivers, as noted by Gordon and Layzer in 1989. Biologists have reported it from depths up to 3 meters. Bottom substrates generally include a mixture of sand and gravel. Because adults do not typically burrow into sediment but rather lies horizontally on the surface, flow refuges may decrease the likelihood of displacement into unsuitable habitat. However, in higher energy habitats where flow refuges are not available along the lower Buffalo River, in Tennessee, biologists have observed this mussel in relatively high concentrations burrowing completely into banks composed of sandy silt.

Food items for mussels include algae, bacteria, detritus and microscopic animals. Adult mussels are filter feeders and generally orient themselves on or near the substrate surface to take in food and oxygen from the water column. Juveniles typically burrow completely beneath the substrate surface and are pedal, or foot feeders, bringing food particles inside the shell for ingestion that adhere to the foot while it is extended outside the shell, until the structures for filter feeding are more fully developed.

Rabbitsfoot shell characteristics include beaks as moderately elevated and raised only slightly above the hinge line. Beak sculpture consists of a few strong ridges or folds continuing onto the newer growth of the umbo, a raised or domed part of the dorsal margin of the shell, as small tubercles, small, rounded projection on surface of the shell. Shell sculpture consists of a few large, rounded, low tubercles on the posterior slope, although some individuals will have numerous small, elongated pustules, noted as small raised spots, particularly on the anterior.

The periostracum, meaning external shell surface, is generally smooth and yellowish, greenish or olive in color. The shell becomes darker and yellowish-brown with age, and is usually covered with dark green, or nearly black, chevrons and triangles pointed ventrally. These patterns are absent in some individuals. Internally, the color of the nacre is white and iridescent, often with a grayish-green tinge in the umbo cavity. Specimens from the southern periphery of its range are occasionally purplish. Soft parts generally have an orange coloration.