Nile monitors may be the largest lizards in Africa, although a former subspecies, now recognized as the species Varanus ornata, can be just as large or larger. Hatchlings are about 30 cm long and weigh around 26 g, but adults can grow to lengths of 2,4 m and have an impressively powerful physique. Sharp claws and strong, muscular legs make climbing trees easy. A deep, robust skull, blunt, crushing back teeth, and an arched lower jaw make it easy for Nile monitors to eat hard-shelled prey such as mollusks. Their tough skin is covered in bead-like scales. They have rounded nostrils that are positioned slightly closer to the front of their noses.
The snout is sharp. The toes are strong and moderately long. The tail of the Nile monitor is laterally compressed with a dorsal keel and a very low double serrated crest.

Nile monitors are generally solitary, with occasional intraspecific interactions outside of the mating season. When inactive, they rest on riparian vegetation, trees, logs, and rocks, often in a prominent position. In the colder regions of South Africa, they hibernate in large crevices or burrows. When walking and foraging, this monitor keeps its body well raised off the ground and uses its long, forked tongue to detect potential food sources.
Nile monitors are usually cautious and, if approached, will either flee or leap into the water, often from a considerable height. They are good swimmers. If cornered and threatened, they arch their backs and stretch out fully on their legs, hissing as they inflate their bodies and thrash their tails sideways. The tail movement can cause painful wounds. As a last resort, a cornered Nile monitor will bite and expel a foul-smelling musk from its cloaca to deter an attack or throw off a pursuer.