In 1511 Joos van Cleve entered the Antwerp guild as a master painter, and in 1520 he was appointed dean of the guild. He received a number of commissions from Cologne, where he influenced the local school of painting. The well-known triptychs of the “Death of the Virgin” (Munich and Cologne), painted for the Hackeney family of Cologne, gave the artist the provisional name of the “Master of the Death of the Virgin” among later art scholars. He is thought to have gone to France as a portraitist to Francis I, and his portrait of Henry VIII suggests that he may have visited England.

Joos van Cleve's work is facile, eclectic, and conservative. He generally altered his style only to agree with the changes in fashion. He is sometimes called “the Elder” to distinguish him from his son, Cornelis van Cleve (1520–67), none of whose paintings survive.