This painting was commissioned in 1483 by the Milanese Confraternity of the Immaculate Conception for their large sculpted altarpiece in their chapel of San Francesco Grande, Milan. It was one of a series of painted and sculpted components of a large altarpiece, which included two paintings of music-making angels, now in the National Gallery, London, reliefs portraying episodes from the life of Mary, sculptures of prophets and a large wooden sculpture of the Virgin.

According to the documents, Leonardo was assisted by the brothers Evangelista and Giovanni da Predis in the execution of the altarpiece. A protracted and complex dispute ensued in 1483 regarding payment, which was not resolved until 1508 with the placement of a second version of this painting, now in the National Gallery, London, in the altarpiece.

The execution of a second version of the painting implies that during the years following its completion, the Louvre version must have been either taken, given away or sold. It is possible that it was sold to a third party, possibly Ludovico Sforza.

The painting portrays the Virgin Mary with her right hand around the shoulders of the infant St. John the Baptist and her left hand over the head of the Christchild. On the right, further towards the foreground, the Christchild makes a sign of blessing towards St. John, while an Archangel, probably Uriel, who is traditionally associated with St. John, points towards St. John with her right hand.

The picture is described as a generic Nostra Donna (“Our Lady”) in the documents, which may provide a clue as to the meaning of the painting. The Virgin is located at the centre of the composition and is portrayed as protector of the young St. John the Baptist, whom Christ is blessing and with whom the Franciscan Confraternity who commissioned the picture particularly identified. The rocky setting in which the figures are situated may have a symbolic meaning that originates from early Christian writings and the Old Testament, where the Virgin is referred to as a rock unhewn by human hands, and the cleft rock as a safe refuge for St. John and Christ during their travels in the wilderness.