The southern leopard frog is one of the 36 species currently or formerly classified in the Rana genus found in North America.

[11] Some larva, eggs and embryos may be exposed to pesticides during their development causing significant mortality and developmental deformity.

[14] This frog lives in many types of shallow freshwater habitat and sometimes in slightly brackish water.

[15] It is usually found close to water, but it can stay on dry land for long periods of time.

[12] During warmer months, it moves away from the water for most of the time,[16] It is mostly nocturnal,[16] but it can be active during the day and the night, especially during rainfall.

[16] It has been shown that L. sphenocephalus eggs hatch more quickly in response to the presence of predators such as crayfish.

[16] In northern parts of its range, it is dormant during the winter, where it remains in well-oxygenated, unfrozen water bodies.

[6] In other parts of their range, their diet consists mainly of spiders, beetles, and gastropods such as snails.

[27] Studies involving southern leopard frogs found that geographically separated populations produce distinct numbers and combinations of antimicrobial peptides (AMPs) in response to growing infection rate of fungal pathogen Batrachochytrium dendrobatidis.