It formed part of a polyptych and was completed in 1469. Unfortunately, the centre panel piece is lost, however the remaining panels, depicting St Augustine, St John the Evangelist and Saint Nicholas of Tolentino, are in museums distributed across Milan, Lisbon, New York and London.

The panel of St Michael depicts the Archangel Michael after vanquishing the armies of the Devil as described in the Book of Revelations, Chapter 12, where he fought the dragon and cast out the slain beast "...that ancient serpent called the Devil..." Saint Michael is shown standing on the decapitated body of the serpent, holding the severed head in his left hand and his sword in his right. He is painted as having the physique of a warrior, with muscular arms and legs, and his torso clad in magnificent armour shows strong anatomical definition.

This theme is prevalent in other works by Francesca, such as The Resurrection, painted around 1463, where Christ is portrayed with an athletic physique and creates a strong image in what is almost a dreamlike scene. However, the panel of Saint Michael is not a painting of war or heroism; it makes a powerful statement with its simplicity and soothing colour palette. There is a gentleness in the facial expression, echoed by the illumination of the wings at his back and the exquisite detail on the red laced boots.

Behind the figure of Saint Michael is only a basic suggestion of architecture but Francesca was a highly skilled painter in this subject matter. A good example of this is the Montefeltro Altarpiece (or the Brera Madonna) from 1474, which shows extraordinary skill and geometric accuracy. Francesca had previously trained in mathematics and was acquainted with the mathematician, Luca Pacioli and architect Francesco di Giorgio Martini, whose iconic designs dominate the city of Sienna. Francesca was interested in geometry and perspective and his talent for this is demonstrated in many of his works. The painting of St Michael is oil and tempera on panel and measures 133cm x 59.5cm. It is now held in the National Gallery, London.