Appleseed Alpha portrays the formative period of Deunan Knute and Briareos in the 22nd century, as they set out across the bleak ruins of New York in search of Olympus. Two Horns, the warlord ruling the decayed city, hires them to destroy bipedal combat units. While fighting, they meet Iris and Olson, who are on a separate assignment. Deunan and Briareos ally with them and agree to join their quest.
Iris must stop the sinister cyborg Talos from seizing a covert weapon humanity is developing. Talos manipulates Iris to trigger the colossal war machine.