Born to a family of gentry, Orzeszkowa was married at age 17 to a landowner. The marriage was unsuccessful, largely because Orzeszkowa not only was passionately and actively pro-independence but also sought the emancipation of the serfs. When it was annulled 11 years later, she settled in Grodno, where in 1879 she opened a bookshop and publishing house. In 1878 she had published Meir Ezofowicz (the name of the protagonist), a novel that presented a lurid picture of Jewish life in a small town in Belorussia and preached not so much tolerance as the assimilation of the Jewish community. The Russian authorities closed down her business in 1882, placing her under police surveillance for five years. She remarried in 1894, but her second husband died two years later.

Orzeszkowa's well-known peasant novels include Dziurdziowie (1885; “The Dziurdzia Family”), which presented a shocking picture of the ignorance and superstition of poor farmers, and Cham (1888; “The Boor”), the tragic story of a humble fisherman's love for a neurotic and sophisticated city girl. Considered Orzeszkowa's masterpiece, Nad Niemnen (1888; “On the Banks of the Niemen,” filmed 1987) depicts Polish society in Lithuania. Bene nati (1892; “Wellborn”) describes the impoverished gentry of small villages.