The painting, commissioned by the Congregation of St Jerome of Charity for the church of the same name in Via Giulia in Rome, was executed by Domenichino between 1611 and 1614. The Bolognese painter had come to this city in 1602 called by his fellow citizen Annibale Carracci, with whom he worked in the Farnese Gallery.
The Communion of St Jerome constitutes his first important recognition in Rome and, except for some rare cases, excited the enthusiastic approval of his contemporaries, who considered it among the masterpieces of Italian art. The subject, which is quite rare, is that of St Jerome who, by now ninety years of age, on the point of death wants to take his last communion surrounded by his disciples and St Paula. Domenichino took his inspiration from a painting with the same subject painted by his master Agostino Carracci ten years previously.