With its short thick head, long ears, thin limbs, small narrow hooves, and short mane, the mule shares characteristics of a donkey; in height and body, shape of neck and croup, uniformity of coat, and teeth, it appears horse-like; the mule comes in all sizes, shapes and conformities. There are mules that resemble quarter horses, huge draft mules, fine-boned racing mules, shaggy pony mules and many more types.

A mule does not sound exactly like a donkey or a horse. Instead, a mule makes a sound that is similar to a donkey's but also has the whinnying characteristics of a horse (often starts with a whinny, ends in a hee-haw). Sometimes, mules whimper. The coats of mules come in the same varieties as those of horses. Common colors are sorrel, bay, black, and grey. Less common are white, roans (both blue and red), palomino, dun, and buckskin. Least common are paint mules or tobianos.

The mule possesses the sobriety, patience, endurance and sure-footedness of the donkey, and the vigour, strength and courage of the horse. Operators of working animals generally find mules preferable to horses: mules show more patience under the pressure of heavy weights, and their skin is harder and less sensitive than that of horses, rendering them more capable of resisting sun and rain. Their hooves are harder than horses', and they show a natural resistance to disease and insects. Many North American farmers with clay soil found mules superior as plow animals.

Mules are generally less tolerant towards dogs than horses are. They are also capable of striking out with any of their hooves in any direction, even sideways if needed.^{[citation needed]}

Mules exhibit a higher cognitive intelligence than their parent species. This is believed to be the result of hybrid vigour, similar to how mules acquire greater height and endurance than either parent.^[8]

Mules are highly intelligent. They tend to be curious by nature. A mule generally will not let the rider put it in harm's way.