Age of Empires III's story campaign unfolds across a series of linked scenarios that follow the fictional Black family through three "Acts," each spanning a different generation and all narrated by Amelia Black. Rather than commanding one of the standard civilizations, players control special factions tied to each Act: the Knights of St. John in Act I, John Black's Mercenaries in Act II, and the United States in Act III.
In Act I: Blood, set in the late 16th century, the Scottish-born commander Morgan Black helps defend the Knights of St. John's last stronghold on Malta against the Ottoman forces of Sahin "The Falcon." When the Turks retreat, Morgan and his superior Alain Magnan uncover ancient writings about the Lake of the Moon — the fabled Fountain of Youth — and a secret society called the Circle of Ossus that covets it. Sent across the Atlantic to find the Lake, Morgan clashes with the pirate Elisabet "Lizzie" Ramsey before washing up in the Caribbean, then fights his way through the New World — destroying an Ottoman base in the Yucatan, allying with the Aztecs, and tangling with the Spanish conquistador Delgado, who seeks the same map.
After capturing Spanish treasure ships and the captive Sahin in Florida, Morgan learns the devastating truth: his own commander, Alain, is the true leader of the Circle of Ossus. At the Lake of the Moon, Morgan, Lizzie, and Sahin seize a massive cannon called the Fixed Gun and use it to hold off the Circle's elite Boneguard, kill Alain, and destroy the Fountain. With the threat ended, Sahin returns to Turkey and Lizzie sails for the Caribbean — and Morgan, left to wonder whether they truly found the Fountain of Youth, quietly refills his canteen from the lake.