Glinda, the Good Witch of the North, announces to the citizens of Oz that Elphaba, the green-skinned Wicked Witch of the West, is dead. We go back in time: young Elphaba and her wheelchair-bound sister Nessarose, daughters of the Governor of Munchkinland, arrive at Shiz University. Elphaba and Glinda clash immediately when Elphaba is invited to join headmistress Madame Morrible’s sorcery class, and Glinda is not. Elphaba, excited and surprised to discover she might have a talent for magic, imagines what it would be like to meet The Wizard.
The students settle into their routine at Shiz: roommates Elphaba and Glinda loathe each other. Glinda and the other students pay little attention to their history professor, Doctor Dillamond, a talking goat. Only Elphaba is troubled by his warning that, throughout Oz, talking animals are losing their ability to speak. Fiyero, a Winkie Prince, arrives at Shiz, and invites Glinda to a dance. To evade her persistent Munchkin admirer, Boq, Glinda convinces him to escort Nessarose. When a grateful Elphaba gets Glinda into sorcery class, Glinda decides to give Elphaba a social makeover.
Elphaba is distraught when Doctor Dillamond is arrested and taken away by the authorities. When she witnesses a government official experimenting on a caged lion cub, Elphaba’s anger releases a spell, freezing everyone in the room. When Elphaba and Fiyero free the terrified lion in the woods, Elphaba learns to her surprise that she is attracted to Fiyero. Madame Morrible informs Elphaba she’s been invited to the Emerald City to meet The Wizard; Elphaba invites Glinda along. Under the pretence of testing her magical skill, The Wizard tricks Elphaba into creating an enchanted army of spies for him.
Elphaba is shocked to realise that The Wizard has encouraged anti-animal sentiment to strengthen his own political support. As Madame Morrible denounces her to the public as a “wicked witch,” Elphaba vows to fight The Wizard’s injustice.
Act II begins with Glinda and Madame Morrible, now part of The Wizard’s administration, announcing Glinda’s plan to marry Fiyero, who is in charge of the hunt for Elphaba. Glinda appears happy, but has paid the price of success. In Munchkinland, Nessarose has become Governor. She has become bitter and cruel, earning her nickname “The Wicked Witch of the East”. Elphaba comes to Nessarose seeking aid and Asylum, but they quarrel and go their separate ways. Elphaba returns to Emerald City, where The Wizard tries to persuade her to join him in ruling Oz; she is tempted, but refuses.
After crossing paths in the Emerald City, Elphaba and Fiyero have fallen in love and plan their life together. Elphaba sees a disturbing vision of a flying house and rushes to Munchlinland, only to discover that Nessarose has been crushed. Glinda and Elphaba confront each other; when Fiyero tries to intervene an angry mob rushes him off. Elphaba vows to become truly Wicked, since her good intentions bring only suffering. Meanwhile, the citizens of Oz set out to destroy her.