The painting comes from the church of San Francesco al Prato in Perugia, but its collocation inside the church changed many times due to provisions of the Council of Trent; during these internal transfers, following an unknown incident, the work suffered damages in the figure of San Sebastiano and perhaps for this reason it was not chosen by the Napoleonic troops during the requisitions. The work originally belonged to the Martinelli family, who commissioned the realization of the panel to Perugino; however, probably the painter had some issues with them, since in 1520 Perugino sued some family members for non-payment. The agreed amount was 90 florins, according to the will of the founder Martinello, who died in 1504 probably due to the plague epidemic unleashed in Perugia; but Vannucci finished the painting only in 1518, as can be read in the inscription on the cornice of the plinth, and maybe this was the reason the family didn’t pay him as agreed. The composition recalls the contemporary Martyrdom of Saint Sebastian in a church not far from Città della Pieve, San Sebastiano in Panicale.