After the death of Feodor Alexeevich, she led a group of Miloslavskii boyars in a struggle for power. On May 29, 1682, she became Regent to Ivan and Peter, and thus effectively the ruler of Russia.

She was extremely active in internal and foreign policy. Russia concluded "The Eternal Peace" with Poland in 1686, and the Nerchinskii Treaty with China in 1689. There were also two military expeditions to the Crimea.

In 1687, the first educational establishment opened in Russia: the Academy of Slavic, Greek and Latin Studies.

In 1689, Sofia was overthrown by supporters of Peter the Great and exiled to the Novodevichii Monastery.

In 1698 she was forced to take the veil under the name of Susanna.