Serao grew up in poverty and worked as a schoolmistress, an experience later described in the preface to a book of short stories called Leggende Napolitane (Napoletan Legends, 1881).
She first gained notoriety after publishing her short stories in Il Piccolo, a newspaper edited by Rocco de Zerbi and her first novel, Fantasia (Fantasy, 1883), which established her as an author capable of writing with sentiment and analytical subtleties.
With her husband, Edoardo Scarfoglio, she founded Il Corriere di Roma, the first Italian attempt to model a daily journal along the lines of the Parisian press.
The paper was short lived, and after its demise Serao established herself in Naples where she edited Il Corriere di Napoli.
The late nineteenth century English novelist George Gissing read three of her works in the original Italian between November 1894 and early January 1895, namely "Gli Amanti", "Cuore Infermo" and "Fantasia".