At the time of his father's death he was a hostage at the court of the Ottoman emperor Beyazid I at Brusa (modern Bursa), but succeeded in making his escape; he was forthwith besieged in Constantinople by the sultan, whose victory over the Christians at Nicopolis, however (September 28, 1396), did not secure for him the capital.
Manuel subsequently set out in person to seek help from the West, and for this purpose visited Italy, France, Germany and England, but without material success; the victory of Timur in 1402, and the death of Bayezid in 1403 were the first events to give him a genuine respite from Ottoman oppression. He stood on friendly terms with Mehmed I, but was again besieged in his capital by Murad II, in 1422. Shortly before his death he was forced to sign an agreement whereby the Byzantine Empire undertook to pay tribute to the sultan.
Manuel was the author of numerous works of varied character — theological, rhetorical, poetical and letters.