The film begins with Lizzie McGuire preparing for her junior high graduation with her best friend, David “Gordo” Gordan. Lizzie trips onstage and accidentally brings the curtains down on her fellow graduates, which causes her to be teased mercilessly by her nemesis, Kate Sanders and her younger brother Matt.
After graduation, Lizzie and her class embark on a trip to Rome chaperoned by their strict high school principal, Ms. Angela Ungermeyer. Lizzie and Kate are assigned to be roommates, much to their dismay.
The class first stops at the Trevi Fountain where Lizzie is approached by Paolo, a famous Italian pop star, who mistakes her for his singing partner Isabella. Paolo asks Lizzie to meet him at the Trevi Fountain the next day and she pretends to be sick in order to sneak away.
He explains that he and Isabella are booked for the Italian Music Awards but Isabella left Italy after their break up. Paolo confides in Lizzie that Isabella lip synchs and begs Lizzie to pose as her for the concert. Lizzie reluctantly agrees but quickly begins to enjoy the life of an Italian pop star with all the designer clothes, dance rehearsals, and adoration from fans.
Lizzie continues to fake being sick in order to spend time preparing for the concert and Kate quickly figures out her secret. Much to Lizzie’s surprise, Kate agrees to help her and the two become closer. Lizzie begins to fall in love with Paolo, much to Gordo’s dismay. Kate and Ethan encourage him to declare his love for Lizzie, but Gordo refuses.
Meanwhile, Ms. Ungermeyer interrogates the students to find out who has been sneaking out. Gordo takes the blame and for his punishment, he is sent back to America. Lizzie is shocked to hear that Gordo gave himself up for her and Kate reveals that Gordo is in love with her.
At the airport, Gordo meets the real Isabella, who has returned for the concert. She and Gordo realize that Paolo is planning to cut Lizzie’s mike at the concert to convince the crowd that Isabella is a fake, which would ruin Isabella’s career and embarrass Lizzie. They rush to the concert to stop Paolo.
Meanwhile, back in America, Matt browses the Internet and finds Italian gossip sites that posted pictures of Lizzie as Isabella. Matt tells his parents and the family flies to Rome to catch her. Ms. Ungermeyer also realizes that Lizzie is missing once again and Ethan accidentally reveals she is at the Italian Music Awards.
The class rushes to the concert to find Lizzie. Gordo and Isabella find her backstage preparing for the show and attempt to warn her of Paolo’s scheme. At first, Lizzie refuses to believe them but Isabella reminds Lizzie that Gordo can be trusted and Paolo is just using her.
When it’s time for the performance, Isabella and Gordo expose Paolo by turning on his microphone, showing his terrible singing voice. Paolo runs off, embarrassed, and is ambushed by the paparazzi outside. His bodyguard, Sergei (Brendan Kelly) tells Paolo that it’s time to face reality and quits to go flirt with Ms. Ungermeyer who has gotten the class as well as Lizzie’s family into the concert by beating up the bouncers.
Isabella then introduces Lizzie to the crowd and has Lizzie sing “What Dreams Are Made Of”. Later, they all celebrate at the after party at the hotel.
Ms. Ungermeyer lifts Gordo’s punishment while Lizzie’s parents tell her that she’s grounded for the rest of the summer. Lizzie and Gordo sneak away from the party to go up to the roof. They promise to never let things change between them and Lizzie kisses him. They then go rejoin the party.