Janis Sarkisian, Damian, and the Show Choir welcome the audience to North Shore High School (“Mean”). Meanwhile, in Kenya (“It Roars”), Cady Heron, Mrs. Heron, and Mr. Heron are preparing to move back to the USA. Cady is welcomed at her new high school by MR. Duvall, the principal, and introduced to Ms. Norbury, her homeroom and AP Calculus teacher (“It Roars – Reprise”).

At lunch, Janis and Damian offer to help Cady figure out where she fits in (“Where Do You Belong?”) when in walk the “The Plastics” – Regina George, Gretchen Wieners, and Karen Smith (“Meet The Plastics – Part 1”). Regina, Queen Bee of the high school, notices Cady and invites her to sit with them at lunch for the week (“Meet The Plastics – Part 2”). Janis hatches a plot for Cady to spy on Regina, with whom she had a mysterious falling-out in eighth grade. Cady reluctantly agrees, and Damian offers one of his pink shirts for her to borrow, since on Wednesdays the Plastics wear pink.

The next day in Calculus, Cady meets Aaron Samuel, Regina’s ex-boyfriend (“Stupid With Love”). Cady confesses to Gretchen that she has a crush on Aaron. Gretchen panics but promises to keep her secret. Kevin G compliments Cady on her math skills, but Regina shoos him away, inviting Cady to her house after school (“Apex Predator”). After school, Regina’s mother Mrs. George welcomes the girls with their old Burn Book, which she found in a closet. After Mrs. George leaves, the girls flip through the book and make fun of Janis. Gretchen is afraid Regina is mad at her (“What’s Wrong With Me?”).

The next day, Cady recounts the evening to Janis and Damian. Cady has a Kälteen bar, used for helping underweight people gain weight, and Janis suggests they feed the bars to Regina. Cady refuses.

Janis and Damian narrate as time moves forward: Cady is pretending to be bad at math to get Aaron’s attention, and he invites her to a Halloween party. Cady is embarrassed to be the only one wearing a scary costume, but Aaron thinks it’s fun, and offers to tutor her. Meanwhile, Regina finds out that Cady has a crush on Aaron, and engineers the situation so that Regina and Aaron get back together, sending Gretchen to deliver the message to Cady. Cady, furious, heads to Janis’s house, and they tell Cady the real story of what happened between Regina and Janis. They plot to take down Regina George (“Revenge Party – Part 1”). First, Cady convinces Regina that the Kälteen bars are for losing weight. Then, they convince Gretchen that Regina is mad at her, and Gretchen reveals that Regina is cheating on Aaron with Shane Oman (“Revenge Party – Part 2”). Cady tells Aaron, expecting him to be grateful, but he isn’t. Ms. Norbury confronts her about her grades, offering her a tutor and jokingly threatening to push her desk away from Aaron’s, saying “I’m a pusher.” Later, at Regina’s house, Cady recounts the whole interaction to Gretchen, who encourages her to write it all down in the Burn Book. Regina is frustrated because none of her clothes fit, but Karen reveals that she’s grouchy because Aaron broke up with her.

Later, at the Winter Talent Show, Regina’s skirt pops off when the safety pin fails (“Rockin’ Around The Pole”). The next day at lunch, Cady turns Regina away from their table, since she’s wearing sweatpants on the wrong day. Gretchen and Karen back up Cady’s decision, and the students of North Shore High imagine a school without Regina’s rule (“Fearless”).

Janis is upset when Cady has a family obligation during her art show. When Gretchen and Karen find out that Cady’s parents will be gone, they convince her to have a small get-together by encouraging her to invite Aaron.

Meanwhile, Regina is obsessively exercising when Mrs. George breaks the news of Cady’s party – and that Kälteen bars are for gaining weight, not losing it.

As Cady’s party spirals out of control (“Whose House Is This?”), she stumbles upon Aaron, and what begins as a heart-to-heart becomes a confession from Cady that she was pretending to be bad at math. Aaron is upset, saying she’s just like Regina, and leaves (“More Is Better”). Janis and Damian arrive and confront Cady for lying.

The next day at school, Regina rips out the pages of the Burn Book and scatters them for everyone to read (“World Burn”), then she tells Mr. Duvall, pretending to have found the pages. Mr. Duvall calls all the Junior girls to the gym, where Ms. Norbury mediates a discussion. Janis tells everyone about Cady’s part in the plot to ruin Regina’s life (“I’d Rather Be Me”). Regina rushes out, and Cady follows her to apologize (“I’d Rather Be Me – Tag), and Regina is suddenly hit by a bus – but she’s okay!

Cady confesses to writing “Ms. Norbury is a pusher.” She’s banned from Spring Fling and suspended.

When Cady returns to school, she apologizes to Ms. Norbury and joins the Mathletes (“Do This Thing – Part 1”). Facing off against Caroline Krafft, Cady wins the competition for the team. Aaron is at the competition, and they reconcile (“Do This Thing – Part 2”). Cady goes to the Spring Fling and apologizes to Regina, who accepts her apology. When Cady is announced as Spring Fling Queen, she apologizes to everyone onstage (“I See Stars”).