The tabletop bronze of a lion attacking a horse exhibits a dramatic life and death struggle typical of the intense emotionalism of early Baroque sculpture. Both the bronze and its pendant, Lion Attacking a Bull, feature a wild beast, the ferocious lion, attacking a domesticated animal and forcing it to collapse. The artist delighted in the power of the animals, whose muscular contortions express their physical struggle and psychological anguish. In Lion Attacking a Horse, the artist emphasized the brutality of the kill, using a circular composition to focus attention on the lion's claws tearing through the horse's hide. Animal subjects were extremely popular in the early 1600s and a genre for which the sculptor, Giambologna, was well known.

Lion Attacking a Horse is based on a fragmentary antique statue now in the Palazzo dei Conservatori, Rome. Many casts of the Lion Attacking a Horse are extant; the Museum's bronze is among the highest in quality of those that survive.