The voice cast includes Ai Kobayashi, Jūrōta Kosugi, Mami Koyama, Yuki Matsuoka, and Toshiyuki Morikawa.

The film, the second adaptation of the manga after the 1988 OVA, tells the story of Deunan Knute, a former soldier, who searches for data that can restore the reproductive capabilities of bioroids, a race of genetically engineered clones.

Deunan discovers from anti-Bioroid terrorist Colonel Hades that Briareos had intentionally allowed his Landmate, a large exoskeleton-like battlesuit, to escape.

Briareos tells Uranus that the Elders manipulated the Army into wanting to destroy the D-Tank, but Athena is trying to prevent them from doing so and protect humanity.

Deunan flies back to Olympus in Yoshitsune's Landmate and uses the Appleseed data to fully restore Bioroid reproductive functions.

As Deunan encounters the Council of Elders, they reveal their involvement in Gilliam's death and also plan to use the D-tank virus to sterilize humans, which will leave the Bioroids the new rulers of Earth.

Athena, stepping in to stop them and announcing that Uranus has surrendered, tells Deunan that the Elders had been acting on their own and had shut Gaia down once they realized humanity had softened their stance against Bioroids.

[8] Anime News Network's Carlo Santos said while the plot is overly generic storytelling, the visual presentation and musical score both stand out and give the film its worth.

[9] Helen McCarthy in 500 Essential Anime Movies noted the use of shading and motion capture in the film, stating that "as good as the technology is, the script doesn't match the 1988 version".

[12] Appleseed (2004) was described by Mark Schilling (The Japan Times) as "innovative use of out-of-the-box animation software to create Hollywood-style effects at a tiny fraction of Hollywood budgets.

"[13] This statement was echoed by Studio Ghibli president Toshio Suzuki who stated that Appleseed would revolutionise the animation business.

[13] A video game adaption based on the film was released as Appleseed EX by Sega, developed by Dream Factory for the PlayStation 2 in February 2007.