The campaign starts with John Black and Ká:nien hunting a deer. When they kill it, they bring it with them and return to the colony of John's uncle, Stuart Black . It is explained that a Cherokee army has attacked them. They stop the Cherokee, and John destroys the Cherokee War Huts. He attempts to negotiate with them, but it turns out that the Cherokee have allied with the British. Soon after, a British Frigate under the command of the British general Warwick attacks the colony and captures Stuart. John then attacks and defeats the British army, but finds that Warwick has captured Stuart. However, Ká:nien also tells him that the British are heading towards his tribe, so the two stop the British from killing his sister Nonahkee and his fellow tribesmen. He and Ká:nien save the tribe and Kanyenke's sister, Nonahkee, destroying Warwick's fort in the process.
Soon, John and Ká:nien ally with the French to destroy the British and they stumble into a marching British army, lead by Colonel George Washington. Washington surrenders to John and explains that Warwick is a traitor to England, because although was sent with other British Explorers, Warwick did not ally with them because he was not interested. Washington soon supports Ká:nien and John with British reinforcements, then later on defeat Warwick's navy and colony, though Warwick manages to escape. Then, the two find out that Stuart was killed by Warwick, and John, wanting revenge, crosses the Great Plains with Ká:nien and stumble into a Lakota village. The natives need help to stop the British from killing all their War Chiefs, so John and Ká:nien help them, while learning that Warwick was the current leader of the Circle of Ossus. The two defeat Warwick once again.
In the act's last phases, John and Ká:nien are in the Rocky Mountains where they find a Circle-controlled town. In desperate need of supplies, John and Ká:nien ambush and capture supply convoys heading towards the town, building up an army to destroy the town before Warwick is able to retaliate. Later on, they encounter Warwick again, who reveals to have allied with the Russians who plan to invade the East Coast to capture the Americas for themselves.
John gives Ká:nien several Miners and asks him to have the miners destroy the ice columns, blocking the passageways and delaying the Russian army from getting through the mountain pass. After the Russians have been stalled long enough, a cinematic occurs where John is at the top of the Rockies and prepares to cause an avalanche to stop the Russian army. Warwick and several Boneguard appear; the Boneguard attempt to shoot at John, but Warwick stops them, for they'd have triggered the remote. John detonates the TNT, sacrificing himself, but also kills Warwick, many Circle members and destroys the Russian army heading eastwards.