Brothers Walter and Gary, residents of Smalltown, are fans of the Muppets, having watched The Muppet Show throughout their youth. Now adults, Gary plans a vacation to Los Angeles with his girlfriend, Mary, to celebrate their tenth anniversary, inviting Walter so he can tour the Muppet Studios. Mary feels Gary's devotion to Walter is detracting from their relationship.
In Los Angeles, the three visit the abandoned Muppet Studios. During the tour, Walter sneaks into Kermit the Frog's office and discovers Statler and Waldorf selling the Muppet Theater to oil magnate Tex Richman and his henchmen Bobo the Bear and Uncle Deadly. After Statler and Waldorf leave, Walter overhears Richman reveal his plan to destroy the theater and drill for oil underneath. Walter explains to Gary and Mary that if the Muppets can raise $10 million by the time their original contract expires, they can repurchase the theater.
Agreeing to stop Richman, they find Kermit and inform him he must organize a telethon to raise the money, which appears difficult since the Muppets have gone their separate ways since the show ended its run. Convinced to try, Kermit sets off with the three to reunite the group. Kermit attempts to dissuade Fozzie Bear from continuing to perform in Reno, Nevada with the Moopets, a tribute group of uncouth Muppet impersonators. Meanwhile, Gonzo has become a plumbing magnate and, despite his initial objection, destroys his business and joins them. Animal is recovered from a celebrity anger-management clinic, before being instructed by his sponsor Jack Black to keep away from drums. The other primary Muppets rejoin through a montage. Later in Paris, the group finds Miss Piggy working as an editor for "plus-sized" fashion at Vogue Paris. Having failed to convince Miss Piggy to return, the group replaces her with Moopet counterpart Miss Poogy.
The Muppets return to Los Angeles and pitch their telethon idea to several television networks, but are rejected. Following a show's cancellation, CDE executive Veronica gives the Muppets a recently vacated two-hour slot in the network's schedule, on the condition that they find a celebrity guest. The Muppets refurbish the theater, but their first rehearsal is unsuccessful and Kermit is unable to contact a celebrity guest. Miss Piggy returns, forces Poogy out, and informs Kermit that she refuses to work with him. Kermit inspires Walter to find his talent and perform in the telethon. Meanwhile, Mary goes sightseeing alone.
Kermit entreats Richman to return their studio. Richman declines and reveals that the Muppets will also lose their trademark names, which he plans to entitle to the Moopets. Unsuccessfully, Kermit returns home and Miss Piggy enlists the remaining Muppets to kidnap Black as a celebrity guest. Meanwhile, after discovering that a devastated Mary has returned to Smalltown, Gary realizes that he must improve his relationship with Mary and follows her back home to reconcile, while Walter discovers he was intended to join the Muppets. The telethon begins and gradually attracts a large audience, with the Muppets raising donations with support from celebrity callers and Jack Black serving unwillingly as host. During the show, Richman cuts the theater's power supply, but Gary and Mary return to Los Angeles and restore the power. Richman then attempts to destroy the theater's television transmitter, but a regretful Uncle Deadly stops Richman. Kermit and Miss Piggy finally reconcile and the Muppets perform "Rainbow Connection" as their final act.
However, the telethon runs short as the $10 million has yet to be collected. Having found his talent, Walter performs a whistling act, which is unanimously praised by the audience. Refusing to lose, Richman disables the telephone lines and evicts the Muppets from the theater, after the latter fall short of their monetary goal. Kermit gathers the group in the lobby and delivers a speech, suggesting that they will restart their career together as a family. Exiting the theater, the Muppets are greeted by a vast gathering of supporters on Hollywood Boulevard. With Gary's encouragement, Walter greets the crowd and is accepted by the Muppets as their newest member. Gary proposes to Mary, Richman returns the theater and naming rights to the Muppets after suffering a head injury, and Kermit and Miss Piggy enjoy their private life.
Who gives the Muppets a vacated two-hours spot in the network's schedule?
CDE Executive Veronica