In 1650, Odescalchi became bishop of Novara, in which capacity he spent all the revenues of his see to relieve the poor and sick in his diocese. He participated in the 1655 conclave. In 1656, with the pope's permission, he resigned as bishop of Novara in favor of his brother Giulio and moved to Rome. While there he took a prominent part in the consultations of the various congregations of which he was a member. He participated in the 1669–70 conclave.