Act One (Germany). At the end of Earth Spirit, Lulu was imprisoned for the murder of her third husband, Dr Schön. Pandora's Box opens with her confederates awaiting her arrival after she has been sprung from prison in an elaborate plot. The lesbian Countess Geschwitz, who remains in love with Lulu, has swapped identities with her and takes Lulu's place in prison, hoping that Lulu will love her in return. Rodrigo Quast, the acrobat, plans to take Lulu away with him as a circus performer but when she arrives, emaciated from the prison regime, he declares her unfit for his purposes. Alwa Schön, the writer, succumbs to her charms, despite her having murdered his father. They leave together.
Act Two (Paris). Lulu and Alwa, now married, are entertaining in their lavish home. All are profiting from investments in the Jungfrau cable-car company. Two characters attempt to blackmail her, since she is still wanted by the German police: Rodrigo the acrobat and Casti-Piani, a white slave-trader who offers to set her up in a brothel in Cairo. The sinister Schigolch, who was Lulu's first patron and may be her father, reappears, and by offering to lure Rodrigo and Geschwitz to his lodgings, promises to "take care of" the threatening Rodrigo. As the police arrive to arrest her, Lulu swaps clothes with a groom and escapes. The Jungfrau share price has meanwhile collapsed, leaving her penniless.
Act Three (London). Lulu is now living in a garret with Alwa and Schigolch and working as a prostitute. Geschwitz arrives with the rolled-up portrait of Lulu as an innocent Pierrot which has accompanied Lulu throughout the action of this play and its predecessor. Lulu's first client is the pious mute Mr Hopkins. Alwa is killed by her next visitor, the African prince Kungu Poti. Another client, the bashful Dr Hilti, flees in horror and Geschwitz tries unsuccessfully to hang herself. 'Jack' (putatively Jack the Ripper), her final client, argues with her about her fee. Geschwitz vows to return to Germany to matriculate and fight for women's rights. Jack murders Lulu and Geschwitz; the latter dies declaring eternal love for Lulu.