Raphael was born in Urbino, a central Italian duchy noted for its elegant gentility and Renaissance scholarship. After training under Perugino, he moved to Florence toward the end of 1504.

A Roman soldier of Christian faith, Saint George saved the daughter of a pagan king by subduing a dragon with his lance; the princess then led the dragon to the city, where the saint killed it with his sword, prompting the king and his subjects to convert to Christianity.

One unusual feature of the painting is the saint's blue garter on his armor-covered leg. Its inscription, HONI, begins the phrase "Honi soit qui mal y pense" or "Disgraced be he who thinks ill of it," the motto of the chivalric Order of the Garter, of which George is the patron saint