Panty and Stocking are sent to investigate several cases of people getting eaten by toilets, which are caused by a ghost bent on covering Daten City in feces.

At the preview of her and Stocking's first feature film, Panty screens a pornographic film she once starred in, which leaks to the public. With her celebrity lifestyle at risk, Panty travels the world with Stocking and destroys every copy of the porn in existence save for one, which the sisters decide to keep for themselves. But when Panty reveals she edited out all of Stocking's scenes in their film, Stocking gets revenge by uploading the last porn copy online.

Panty and Stocking get into a heated argument over a missing cup of pudding and go their separate ways. However, they are forced to put their differences aside to defeat a pair of Ghosts who work as a team.

Stocking finds herself gaining weight and goes on an intense diet, but she only keeps getting fatter until she balloons into a giant. When the cause is revealed to be from an obese Ghost who refuses to diet, Stocking sets out for revenge. Upon defeating the Ghost, Stocking returns to her original figure.

A recreational nose-picking fad spreads across Daten City thanks to a man named Oscar H. Genius, who invites the citizens of Daten City to a blimp party. However, Genius turns out to be a Ghost intent on ramming the blimp into the moon using the passengers' collective nosebleeds.

Panty and Stocking arrive at school to find that a strict academic regime has been established by the mayor's daughters, the Demon sisters Scanty and Kneesocks, and are banished to the lowest class in school. Together with Brief, Panty and Stocking discover that Scanty and Kneesocks are demons who are running a factory that produces an army of fake Ghosts beneath the school. A destructive battle ensues, with the Anarchy sisters defeating the Daemon sisters by destroying the stone that powers the factory.

Panty and Stocking's sibling feud escalates into all-out war when they eat the cores of two warring alien robots and transform into robots themselves. When the alien robots decide to join forces to destroy the human race and merge into a Ghost, Panty and Stocking are once again forced to work together to defeat the Ghost.

Daten City High School holds a lingerie run in which participants must race in their underwear. The run is interrupted by a Ghost who eats underwear, including Panty and Stocking's weapons, so Panty must resort to using whatever underwear she can find.

Stocking falls in love with a repulsive and ill-mannered Ghost and is willing to forsake her duties as an angel in order to be with him. Concerned for her sister, Panty attempts to kill the Ghost, but the Ghost proves to reciprocate Stocking's feelings and proposes to her. The moment Stocking accepts, however, the Ghost finds himself at peace and ascends to Heaven.

The second part is a trilogy of shorts starring Panty and Stocking's pet sidekick, Chuck.

Panty and Stocking suspect Garterbelt of engaging in sexual activities behind their backs and search for incriminating evidence to use against him. They instead find Garterbelt's diary, which details his past life as a crime lord before he was killed and forced by God to live through all of history until he agreed to become His missionary.

Panty and Stocking have collected enough Heaven Coins to be allowed back into Heaven. However, only Stocking is taken back while Panty is forced to repeat her duties on Earth and forbidden to have sex as punishment for her immoral behavior. To cheer her up, Brief invites her to a party where he is to be engaged to the mayor's daughter (Scanty in disguise) and instead announces his intention to marry Panty. Scanty and Kneesocks attack Panty, who begins losing her angelic powers and escapes with Brief. Panty decides to have sex with Brief, but finds herself unable to do so as she has regained her virginity. Corset and the Demon sisters appear and kidnap Brief, the blood kin of Hell's Monkey whose penis is the key to Hell's Gate, leaving Panty powerless to save him.

Having lost her powers, Panty is kicked out by Garterbelt and moves onto a farm with an old woman who, unbeknownst to her, is in league with Garterbelt and persuades her to stop Corset from using Brief to unlock Hell's Gate. Panty has sex with Brief, losing her virginity and restoring her powers. Stocking returns to help Panty fight Corset and the Demon sisters.