

These third-person perspective elements were compared by several reviewers to Gears of War, in that the player can have Drake take cover behind walls, and use either blind fire or aimed fire to kill enemies. Grenades are also available at certain points, and the height of the aiming arc is adjusted by tilting the Sixaxis controller up or down. Picking up a different firearm switches that weapon for the new one. Nate can only carry one pistol and one rifle at a time, and there is a limited amount of ammunition per gun. Melee attacks comprise a variety of single punches, while combo attacks are activated through specific sequences of button presses that, when timed correctly, offer much greater damage the most damaging of these is the specific 'brutal combo', which forces enemies to drop twice the ammunition they would normally leave.

When facing enemies, the player can either use melee and combo attacks at close range to take out foes or can opt to use weapons. Nate discovers that the idol is located near the customs house, and finds and rescues Sully, who survived being shot from the Drake's old diary blocking the bullet. After finding old records showing the statue was moved further inland, they find that Sully has survived his gunshot wound. Briefly captured by pirates led by old associate Eddy Raja, Elena breaks Nate free and they flee to the old customs house on the island. After retrieving supplies from Sully's destroyed plane, Nate heads toward an old Spanish fort to find Elena. On the way to the island, anti-aircraft fire forces Elena and Nate to bail out of the airplane and they are separated. Sully is shot in the chest, but Nate manages to escape to an island where Sir Francis Drake's diary claims the idol is located.

After finding a U-boat, mercenaries led by criminal Gabriel Roman and his lieutenant Atoq Navarro intercept Nate and Sully.

When Sully and Nate follow the diary to the indicated spot, they learn that El Dorado is a large golden idol rather than a city that the Spanish had tried to remove from the island centuries ago.
