Educated at Straight University (now Dillard University), she worked as a teacher and journalist before marrying the renowned poet Paul Laurence Dunbar in 1898. Their troubled marriage ended in 1902, after which she continued to build her own distinguished career. She later became an active advocate for women's suffrage and African American civil rights.
Her first book, Violets and Other Tales (1895), a collection of poetry and prose, established her as a promising young writer. Her most celebrated work, The Goodness of St. Rocque and Other Stories (1899), vividly portrayed Creole life in New Orleans, blending realism with local color. She also edited anthologies including Masterpieces of Negro Eloquence (1914) and The Dunbar Speaker and Entertainer (1920), and wrote the play Mine Eyes Have Seen (1918).
Dunbar-Nelson's diaries, later published as Give Us Each Day, remain valuable records of African American women's lives. She is regarded as an important precursor to the Harlem Renaissance.