She was the elder daughter of Tsar Alexis and his second wife, Natalia Naryshkina, and the sister of Peter the Great.

Natalia shared the difficulties of her mother and brother during the regency of her half-sister, Tsarevna Sophia.

She shared Peter's wish to reform Russia to a Western country, it was said that "she loved everything that her brother liked", and she supported his ideas from their childhood.

She was young when Peter instituted his Western reforms, and in contrast to her half-sisters, it was not hard for her to adjust to the new ideals.

It was at her court that Peter met his lovers Anisya Kirillovna and Varvara Michajlovna Arsen'eva.