Having lived in seclusion most of his life, Mehmed Reşad became sultan after his brother Abdülhamid II was forced to abdicate. A kind and gentle man, educated in traditional Islāmic subjects and Persian literature, he showed a keen interest in Ottoman and Islāmic history; nevertheless, he lacked the ability to govern. Attempting to rule as a constitutional monarch, he surrendered all authority to the Committee of Union and Progress, the liberal–nationalist organization of the Young Turk movement.

On the advice of the committee, the Sultan went on a goodwill tour of Thrace and Albania (1911). In the two Balkan Wars during 1912–13, however, the Ottomans lost almost all their European possessions, and, in the war with Italy (1911–12), Tripoli was lost. Although Mehmed was opposed, the Ottoman Empire entered World War I on the side of Germany and Austria-Hungary, and, as caliph, he declared holy war and invited all Muslims, especially those under the rule of the Allies, to rally to the support of Ottomans. By the time of Mehmed's death, most of the empire had fallen to the Allies, and six months later Constantinople was under military occupation.