His style is defined by a meticulous attention to small details and a specific way of painting the sky. Mostaert often used a very fine brush to create tiny figures in his backgrounds. These figures move through scenes filled with rocky cliffs and villages bathed in a soft blue haze. His clouds are easily identified by their regular, scalloped edges against the sky. In works like The Adoration of the Magi, he placed traditional religious figures within contemporary architectural settings that featured miniature grisaille narratives.

Modern collectors value the storytelling found in the secondary scenes of his panels. He often divided his compositions into a main subject and a separate background space that contained a different, related story. His portraits, such as Portrait of a Man, offer a sense of quiet dignity. These paintings function as windows into the sixteenth-century world, combining formal courtly style with a curiosity about the wider earth.