A nobleman whose clan descended from the 14th-century Lithuanian grand duke Gediminas, Golitsyn became a court chamberlain (1676) and Peter's tutor. Although Peter's half-sister, the regent Sophia Alekseyevna (ruled 1682–89), favoured him with an appointment as head of the government department that administered the lower Volga region, his political sympathies lay with Peter and his family, the Naryshkins.

In 1689 he participated in the coup d'etat that removed Sophia and placed Peter on the throne; with several other advisers to the Naryshkins, he unofficially assumed control of the government. In 1690 he was made a boyar (next in rank to the ruling princes) and subsequently was closely associated with the major achievements of the early period of Peter's reign—the exploratory expeditions in the White Sea (1694–95), the military campaigns against the Turks at Azov (1695–96), and the shipbuilding projects on the Don River (1697). While Peter was travelling in western Europe (1697–98), Golitsyn remained in Moscow, acting (with two others) as head of state; in 1698 he participated in the suppression of the revolt led by Sophia and urged the severe punishment of her supporters. After the Russian army was badly defeated by the Swedes at Narva (November 1700), Golitsyn helped rebuild it by recruiting and training 80,000 new dragoons. But he ruled his province on the lower Volga despotically, and in 1705 his misrule resulted in a major revolt in Astrakhan. Despite his long years of faithful service, Peter relieved him of his duties.