After the master's death in 1520, Penni worked together with other members of Raphael's workshop to finish the commission to decorate with frescoes the rooms that are now known as the Stanze di Raffaello, in the Apostolic Palace in the Vatican. The Baptism of Constantine is located in the Sala di Costantino ("Hall of Constantine"). In the painting emperor Constantine I is seen shortly before his death, kneeling down to receive the sacrament from Pope Sylvester I in the Baptistery of the Lateran. The painter has given Sylvester the traits of Clement VII, the Pope who had ordered the frescoes to be finished, after the work was interrupted during the papacy of Hadrian VI.
While attempting the control and serenity typical of the High Renaissance, the crowded scene demonstrates the Mannerist tendency towards complexity and discordance.