The painting is signed under the seated emperor OPVS PETRI DE BVRGO S[AN]C[T]I SEPVLCRI – "the work of Piero of Borgo Santo Sepolcro" (his native town).
The Flagellation is particularly admired for the mathematical unity of the composition, and Piero's ability to depict the distance between the actual flagellation scene and the three characters in the foreground realistically through perspective. The portrait of the bearded man on the left is considered unusually intense for Piero's time.
Much of the scholarly debate surrounding the work concerns the identities or significance of the three men in the right foreground, and of the sitting man on the left, who is in one sense certainly Pontius Pilate, a traditional element in the subject, but may also represent a contemporary figure.
It has also been suggested that there can be multiple identities for each man depending on how it is read. The interior scene is illuminated from the right while the "modern" outdoor scene is illuminated from the left. Originally the painting had a frame on which the Latin phrase "Convenerunt in Unum" ("They came together"), taken from Psalm 2, ii in the Old Testament, was inscribed.
The seated man on the far left watching the flagellation would be the Byzantine emperor John VIII Palaiologos, as identified by his clothing, particularly the unusual red hat with upturned brims which is present in a medal by Pisanello. In the variant of this interpretation, proposed by Carlo Ginzburg in 2000, the painting would be in fact an invitation by Cardinal Bessarion and the humanist Giovanni Bacci to Federico da Montefeltro to take part in the crusade. The young man would be Bonconte II da Montefeltro, who died of plague in 1458. In this way, the sufferings of Christ are paired both to those of the Byzantines and of Bonconte.
Silvia Ronchey and other art historians agree on the panel being a political message by Cardinal Bessarion, in which the flagellated Christ would represent the suffering of Constantinople, then besieged by the Ottomans, as well as the whole Christianity. The figure on the left watching would be sultan Murad II, with Constantine VIII on his left. The three men on the right are identified as, from left: Cardinal Bessarion, Thomas Palaiologos (Constantine VIII's brother, portrayed barefoot as, being not an emperor, he could not wear the purple shoes with which Constantine is instead shown) and Niccolò III d'Este, host of the council of Mantua after its move to his lordship of Ferrara.
Piero della Francesca painted the Flagellation some 20 years after the fall of Constantinople. But, at the time, allegories of that event and of the presence of Byzantine figures in Italian politics were not uncommon, as shown by Benozzo Gozzoli's contemporary Magi Chapel in the Palazzo Medici-Riccardi in Florence.
The interior scene represents Pontius Pilate showing Herod with his back turned, because the scene closely resembles numerous other depictions of the flagellation that Piero would have known.
Lavin identifies the figure on the right as Ludovico Gonzaga, Marquis of Mantua, and the figure on the left as his close friend, the astrologer Ottavio Ubaldini della Carda, who lived in the Ducal Palace. Ottavio is dressed in the traditional garb of an astrologer, even down to his forked beard. At the time the painting is thought to have been made, both Ottavio and Ludovico had recently lost beloved sons, represented by the youthful figure between them. Note that the youth's head is framed by a laurel tree, representing glory. Lavin suggests that the painting is intended to compare the suffering of Christ with the grief of the two fathers. She suggests that the painting was commissioned by Ottavio for his private chapel, the Cappella del Perdono, which is in the Ducal Palace at Urbino and which has an altar whose facade is the exact size of the painting. If the painting was on the altar, the perspective in the painting would have appeared correct only to someone kneeling before it.
As a young man St Jerome dreamt that he was flayed on divine order for reading pagan texts, and he himself later recounted this dream, in a celebrated letter to Eustochium, in terms that exactly correspond with the left-hand side of the Urbino panel.
Pope-Hennessy also cites and reproduces an earlier picture by Sienese painter Matteo di Giovanni, which deals with the subject recorded in Jerome's letter, helping to validate his identification of Piero's theme.