The Cuban tree frogs range in size from 3 to 5.5 inches (76 to 140 mm) in length. It is the largest tree frog in North America and has a rough warty skin. Their toepads are much larger than those of other tree frogs and they will often have an orange-tint to their eyes. Varying in color from, olive-brown, bronze, gray, or grayish-white. Cuban tree frogs can change colors depending on their temperature and environment. Many individuals have darker splotches on the back, and some splotchy banding on the legs. In many individuals, the hidden surfaces of the legs are bright yellow. When the frog leaps to avoid a predator, these bright yellow patches are visible, and may help to confuse the predator. Also, the skin on their heads is fused to the skull—if the head of an adult frog is rubbed (between the eyes), the skin does not move. This is a special adaptation that prevents water loss, since there are fewer blood vessels in the "co-ossified" (fused) area. When handled, Cuban tree frogs secrete a toxic mucus from their skin. In humans, this can cause an allergic reaction or burning sensation to the eyes and nose, and even trigger asthma.
Cuban tree frogs are known to inhabit a variety of communities, including estuarys, low-density suburban development, small towns, agricultural areas, particularly ones with exotic plants, and lowland forests and swamps. Within their habitat they can be found in damp, shady areas, particularly around shrubs and trees, by cisterns, rain barrels, and buildings.