He studied painting with his father, Valentine van Orley. The young man went from his native Brussels to Rome. From 1509 to 1515 traveled to Italy. In Rome, he could learn from Raphael, in any case — he certainly experienced the strong influence of this painter.
Returning to the Netherlands, he supervised on behalf of Pope Leo X for manufacturing the famous tapestry series "Acts of Sts." At the Van Aalst weaving factory in Brussels. Apostles "on the cardboards of Raphael. In addition, Van Orley himself was engaged in the manufacture of cartons for tapestries: "The Hunt of Emperor Maximilian" (Louvre), "The Life of Abraham" (Hampton Court, London). He also created drawings for painted window glass: "The Emperor Charles V and his sister Maria Hungarian" (St. Gudula Church, Brussels).