The original cast included Michael Mohun as Valentius, Edward Kynaston as Florus, Richard Bell as Honorius, Edward Lydall as Statilius, William Beeston as Macrinus, Rebecca Marshall as Fulvia, Elizabeth Knepp as Antonia, Marmaduke Watson as Hostilius, William Cartwright as Arsenius, Elizabeth Boutell as Aurelia and Katherine Corey as Sophonia.

The Emperor of Rome, Valentitius, is at war with his brother, who has attempted to usurp the throne.

Upon discovering that her father lied to her in the hopes that she would cease to pursue Florus, she murders him.

Afterwards, Sophonia, the Emperor's first wife- who, after being wrongfully accused of adultery, has been posing as the handmaid of Aurelia- commits suicide and leaves a note revealing her innocence as well as the fact Florus was her son, whom she, fearing that her own disgrace would endanger his life, passed off as a friend's child.

William Joyner states in his preface that The Roman Empress is partially modeled after Oedipus and Phaedra.