The year is 2011, and the world has largely forgotten the Muppets. In Smalltown, USA, , the world’s biggest Muppet fan, lives with his human brother, Gary (Jason Segel), and Gary’s girlfriend, Mary (Amy Adams).

The group sets off on a cross-country montage to find the gang:

Panic-stricken, Walter finds Gary and Mary, and they track down , who is living in a lonely mansion. Kermit realizes that to save the studio, they have to "get the Muppets back together."

As the telethon begins, the Muppets struggle to find their rhythm, and the donations trickle in slowly. At the last minute, Miss Piggy returns, and the show catches fire. They perform "The Muppet Show Theme" and "Rainbow Connection," bringing the world back to its senses.