On April 8, 1906, Capotosti was appointed Bishop of Modigliana by Pope Pius X, receiving his episcopal consecration on the following May 31 from Archbishop Carlo Castelli, OSC.
As Secretary, Capotosti served as the second-highest official of that dicastery, successively under Cardinals Filippo Giustini and Michele Lega.
Pope Pius XI created him Cardinal Priest of San Pietro in Vincoli in the consistory of June 21, 1926.
He was papal legate to the Regional Eucharistic Congress in Piacenza on July 30, 1933, and Camerlengo of the Sacred College of Cardinals from April 1, 1935 to June 15, 1936.
He was buried in the crypt of the Sacred Congregation of Propaganda Fide at the Campo Verano cemetery before his remains were relocated to the parish church of Moresco in Ascoli Piceno.