When warring robots from outer space land in Daten City, Panty & Stocking eat their cores and become robots themselves to carry out their sibling feud.

Panty and Stocking get shrunk by some heavenly drugs and end up stuck inside Brief's body.

Panty and Stocking find Garterbelt's diary and learn of his past life as a crime lord before going through several trials set by God.

After collecting the necessary Heaven Coins, Stocking manages to return to Heaven. However, due to her erratic sex life, Panty is forced to stay behind and redo her quota, with Garterbelt forbidding her from having sex. She and Brief go to a party, where a devious plan is being concocted by Corset and the Sisters, and Panty finds herself losing her angelic powers.

Panty is kicked out by Garterbelt for the loss of her powers, but he secretly helps persuade her, with assistance from her grandmother, to stop Corset from using Brief to unlock Hell's Gate using Hell's Monkey. Panty has sex with Brief, breaking her hymen and restoring her powers. Stocking returns from Heaven and helps Panty take on Corset and the demon sisters.

Brief falls onto Hell's Gate and accidentally unlocks it with Hell's Monkey, unleashing a massive Ghost that begins destroying Daten City. Corset fights and kills Garterbelt and proceeds to merge with the Ghost and try to invade Heaven. Panty and Stocking find a credit card hidden in Garterbelt's afro and use it to buy a device that summons their mother, who seemingly destroys Corset and forces the Ghost back into Hell's Gate, which is sealed by Chuck. Garterbelt returns to life in order to continue watching over Panty and Stocking, who are forced to remain on the surface again due to maxing out his credit card. As soon as they return home, Stocking promptly slices Panty to pieces, revealing herself to be a demon working with Corset, who respawns from Brief's penis.