Ypsilantis was born in 1793 in Constantinople, the second son of Prince Constantine Ypsilantis. He studied in Military academies in France before joining the Imperial Guard of the Tsar in St Petersburg. He distinguished himself as a Russian officer in the campaign of 1814, and in the spring of 1821 went to Morea, where the Greek War of Independence had just broken out.
He was one of the most conspicuous of the Phanariot leaders during the earlier stages of the revolt, though he was much hampered by the local chiefs and by the politicians headed by Alexandros Mavrokordatos.
In January 1822 he was elected president of the legislative assembly but the ill-success of his campaign in Central Greece and his failure to obtain a commanding position in the national convention of Astros, led to his retirement early in 1823.
In 1828 he was appointed by Governor Ioannis Kapodistrias commander of the troops in East Hellas. He succeeded, on the September 25, 1829, in forcing the Turkish commander Aslan Bey to sign a capitulation after the Battle of Petra, which ended the active operations of the war.
The city of Ypsilanti, Michigan in the United States of America is named after him.