The earliest representation of the Madonna and Child may be the wall painting in the Catacomb of Priscilla, Rome, in which the seated Madonna suckles the Child, who turns his head to gaze at the spectator. The earliest consistent representations of Mother and Child were developed in the Eastern Empire, where despite an iconoclastic strain in culture that rejected physical representations as "idols", respect for venerated images was expressed in the repetition of a narrow range of highly conventionalized types, the repeated images familiar as icons (Greek "image"). On a visit to Constantinople in 536, Pope Agapetus was accused of being opposed to the veneration of the theotokos and to the portrayal of her image in churches. Eastern examples show the Madonna enthroned, even wearing the closed Byzantine pearl-encrusted crown with pendants, with the Christ Child on her lap.

In the West, hieratic Byzantine models were closely followed in the Early Middle Ages, but with the increased importance of the cult of the Virgin in the 12th and 13th centuries a wide variety of types developed to satisfy a flood of more intensely personal forms of piety. In the usual Gothic and Renaissance formulas the Virgin Mary sits with the Infant Jesus on her lap, or enfolded in her arms. In earlier representations the Virgin is enthroned, and the Child may be fully aware, raising his hand to offer blessing. In a 15th century Italian variation, a baby John the Baptist looks on.

Late Gothic sculptures of the Virgin and Child may show a standing virgin with the child in her arms. Iconography varies between public images and private images supplied on a smaller scale and meant for personal devotion in the chamber: the Virgin suckling the Child (such as the Madonna Litta) is an image largely confined to private devotional icons.

That Mary was the Mother of God is clear from the Gospels, and the theological implications of this were defined and confirmed by the Council of Ephesus (431). Different aspects of Mary's position as mother have been the subject of a large number of works of Catholic art.

There was a great expansion of the cult of Mary after the Council of Ephesus in 431, when her status as Theotokos was confirmed; this had been a subject of some controversy until then, though mainly for reasons to do with arguments over the nature of Christ. In mosaics in Santa Maria Maggiore in Rome, dating from 432-40, just after the council, she is not yet shown with a halo, and she is also not shown in Nativity scenes at this date, though she is included in the Adoration of the Magi.