It is the 22nd Century, the Third World War (2099-2126) has decimated a large part of Earth even though nuclear weapons have not been employed during the conflict. Old nations such as England, France and China have survived but have difficulty restoring their power. On the other hand, new nations and organizations such as the Sacred Republique of Mumna and the Poseidon Organization have been born on the ashes of the world resulting from the Third World War.

In this bleak future, we are introduced to ex-L.A. SWAT members Deunan Knute and Briareos Hecatonchires. Having survived the world conflict and living in a desolated city, they are found by a young woman called Hitomi who proposes them to follow her to the utopian city of Olympus which has become the world's most powerful organization and which registers the new relations in terms of politics, economics and military between new and old nations/organizations. In Olympus, they are integrated in the prestigious ESWAT (Extra Special Weapons And Tactics) organization, whose main mission is to protect Olympus from terrorist attacks and Olympus's interests in the world.

From here on, the two main protagonists encounter a great number of other characters and organizations who will be implicated in international plots that target Olympus.

Appleseed was published in English in-print and digitally by Dark Horse Comics from November 7, 2007 to March 11, 2009 and on September 10, 2014, respectively.