In 1509, the king of France sent him to Rome as his ambassador to the Holy See. He opted for the titular church of San Vitale on 7 November 1509. Following the arrest of Cardinal François Guillaume de Castelnau-Clermont-Ludève on 29 June 1510, Cardinal de Prie left Rome along with other prelates loyal to Louis XII. During the War of the League of Cambrai, he accompanied Louis XII in his expedition against Milan in October 1510, in direct violation of the pope's orders. On 17 March 1511 he opted for the titular church of Santa Sabina. Pope Julius II deposed him as a cardinal on 24 October 1511 and excommunicated him for his role in organizing a schismatic council at Pisa that opened on 1 November 1511. On 10 January 1512 he wrote to the University of Paris in opposition to writings by Thomas Cajetan attacking Jean Gerson.