Rise and Fall includes two campaigns, which are divided into acts containing from two to four chapters each; a chapter comprises a battle and a cinematic. The first campaign follows Alexander the Great on his quest to defeat the allegiance of his brother, and the Persian general, Memnon. The second campaign features Cleopatra, and her attempts to repel a Roman invasion by Octavian.

The Alexander the Great campaign recounts the young king’s conquest of Asia. The beginning cinematic is of the killing of Philip II of Macedon, Alexander’s father, and introduces Alexander as a naive and unprepared prince, who is challenged by the duties thrust upon him. Alexander decides to follow the advice of his tutor, Aristotle, by quelling rebellions in Greece and its territories, as well as forming an allegiance with Parmenion. He then follows his brother—who had left to Persia—by sea, and faces off against the army and navy of General Memnon. Captured by deceit, Alexander escapes, but only after fighting in an amphitheatre. He then begins to sack Persian cities, and takes a temple containing the Bow of Heracles, a mythical weapon of immense power. Alexander eventually captures his brother, and executes him for treason. Finally, during the Siege of Tyre, Alexander defeats Memnon, and is portrayed as having earned his kingdom. By now, Alexander has matured, and his men hold him in high esteem.