He was born early in the 14th century to a family of court dignitaries in Moscow. Despite a fine education, he was not drawn to worldly success and became a monk at the age of twenty. In time Alexis was consecrated Bishop of Vladimir, then Metropolitan of Moscow, at that time the highest rank in the Russian church (which was still under the Patriarchate of Constantinople). Russia was then under the cruel domination of the Tatars. Saint Alexis traveled twice to the Golden Horde, where the Tatar Khan kept court. On his first visit (1359), he healed the Khan's wife of a blindness which had afflicted her for three years — a miracle that did much to soften the Tatars' treatment of their Russian vassals, and to preserve the liberty of the Church.

His ceaseless labors in the world did not deprive the Saint of his love for monasticism: he conferred with holy monks at every opportunity, and founded many new monasteries. As he neared the end of his life he tried without success to persuade his friend St Sergius of Radonezh (September 25) to succeed him. He reposed in peace in 1378. His incorrupt relics are venerated in the Cathedral of the Theophany in Moscow.