The show began with Timberlake descending from the ceiling on a large orange Nickelodeon blimp, and breaking into a Broadway show tune in which he taunted the audience, saying he was too famous to be slimed.
"You'll never get a drop of slime on old J.T.," he sang.
Chris Tucker, Jackie Chan, Mandy Moore, Timberlake and dozens of extras were covered in green goo within minutes, much to the delight of the screaming kids in the audience.
Those stars join a list of past celebrity sliming victims during the popular ritual in which gallons of slime rain down on someone during the festivities. Other previous recipients of the honor have included Tom Cruise, Jim Carrey, Will Ferrell, Mike Meyers and Pink, the latter being the only person for whom pink goo was substituted.
The annual awards show always draws A-listers to what's become Hollywood's messiest, most raucous celebration honoring kid viewers' personal picks for best movies, music and TV shows.
"Every celebrity that's showing up better have eyes in the back of their head because there will be slime," said Timberlake.
The show featured plenty of gross-out humor, including the presentation of one award where the name of the winner was revealed by a presenter pulling a long "booger" out of a giant nose.
There was also the annual burp contest, which had an added twist this year, pitting two-time champion Timberlake against all 12,000 people in the audience at Pauley Pavilion. The crowd burped simultaneously in a mass burp that sounded like it was augmented by special-effects. Timberlake was roundly defeated.
Winners announced during the show that included a 23-story bungee jump into a giant vat of green slime included Adam Sandler as favorite male movie star, Dakota Fanning as favorite female movie star and Ben Stiller as winner of the night's top honor, the Wannabe Award, for the celebrity kids most want to be like.
2"I can't believe this, oh my goodness," said Fanning, who giggled her way through her acceptance speech. "I want to thank all of you out there, and at home, who voted for me. "I consider all of you my friends!"
In a speech mocking awards speeches, Sandler put on his "Happy Gilmore" voice as he thanked the inventor of the potato chip bag and the pillow, and everyone in the audience "for not making fun of me for talking like this every speech I do."
The show closed with Vince Vaughn and Timberlake being soaked in slime again. When the audience roared its approval, they pulled out firehoses and sprayed hundreds of people in the audience that included such celebrities as Steven Spielberg, Nicole Kidman, Queen Latifah and numerous others.
The Kids' Choice Awards is carried live to the East Coast from UCLA's Pauley Pavilion on the Nickelodeon cable network, and taped for broadcast on the West Coast as well as Europe, Russia, Israel, Asia, Australia and Latin America.
Kids vote online to select the winners in each category. Approximately 25 million votes were cast last year, according to Nickelodeon.
20th Annual Kids' Choice Awards Winners List
"The Pirates of the Caribbean: Dead Man's Chest"
Favorite Female Movie Star
Favorite Male Movie Star
Favorite Voice from an Animated Movie
Queen Latifah/"Ice Age: The Meltdown"
Favorite Animated Movie
Favorite Music Group
Black Eyed Peas
Favorite Female Singer
Favorite Male Singer
Favorite TV Show
Favorite Television Actress
Miley Cyrus/"Hannah Montana"
Favorite Television Actor
Drake Bell/"Drake & Josh"
Favorite Video Game
"SpongeBob SquarePants: Creature from the Krusty Krab"
"Harry Potter" (series)