Ryan, Winnie the Pooh, Ash Ketchum, Littlefoot, Spongebob, Skipper, The Fantasy Adventure Team, Bobby, Cindy, Greg, Marcia, Peter, Jan, Oliver, Millicent, DJ, Stephanie, Michelle, Alex, Nicky, Malcolm, Mallory, Reese, Renee, Dewey, Daisy, Emily Yeung, Daniel Cook, the Jungle Adventure Crew, the Madagascar Crew, the cubs, Aladar, Taran, Jesse, Mikey, Bloom, The characters of Diary of a Wimpy Kid and the rest of the characters meet Dennis Mitchell is a five-year-old boy who lives with his parents Henry and Alice, and is the bane of next door neighbor George Wilson's existence. The movie opens with George getting the newspaper, but flees inside at the sound of Dennis on his bicycle. He gets into his bed, pretending to sleep as Dennis comes inside to the bedroom, concluding George is sick, and then proceeds to shoot an aspirin down George's throat, because he didn't want to get bitten. George, now choking, spits out the aspirin as Dennis returns home. With his parents both busy, Dennis is forced by his mother into joining his friend, Joey, at Margret's house, who's mother volunteered to watch them for the day. Dennis begs not to, as Margret is mean to him. When they arrive, Dennis, Joey, and Margret venture into the woods to an abandoned tree house and intend to fix it up. Later, while getting paint from a high self in the garage, Dennis tries to grab his sling shot, which was taken away from him, accidentally spilling the paint on the ground. While using a vacuum to clean it up, he also sucks in a few twigs when he goes outside, causing a blockage, switching the suction from 'in' to 'out', a blob of paint and twigs flies into George's grill, which he is using to barbecue lunch.While all of this and the rest of the events in town go on, a burglar named Switchblade Sam (said name not mentioned in the film, only in the end credits) arrives in town and begins robbing houses, as well as striking fear into the children that he meets. Because of his trouble-making but unintentional behavior, his parents often struggle to find suitable babysitters to deal with him. On one night, they manage to get one named Polly and her boyfriend Mickey to babysit him, but repeated doorbell pranks from him push the two too far (not knowing he is behind this), and they end up pulling a prank on George when he rings the doorbell to scold Dennis after finding paint and wood in his food from the earlier incident.Dennis' parents are both called away on business trips at the same time, and when everyone they know refuses to look after him, they turn to George and his wife Martha (who loves Dennis and sees him as a surrogate grandson, as they never had children) to look after him. George is further irritated by him spilling bath water on the bathroom floor, swapping chemicals with medicine, and bringing his pet dog, Ruff, into the house for a while. Dennis also witnesses George's collection of gold coins, in a bookshelf safe, which uses the houses address as a combination lock. All of this is happening around the time the Summer Floraganza, a long-awaited event, is scheduled to happen. As a longtime member of the local garden club, George is chosen to host it. He is excited to have this honor, as he has been growing and nurturing a rare, night blooming mock orchid for forty years. George notes that after growing for the said length of time, the plant's flower will finally bloom, only to die several seconds later.Alice gets stuck at the airport due to a storm, thus forcing Dennis to stay with the Wilsons for an extra night, which coincides with the unveiling of the plant and its one-time blooming to the members of the garden club. While that is happening, Dennis is sent away for causing trouble. (Curious, he had pushed a black button, which he found out opened the garage door, causing the dessert table that was in front of the garage door to be overturned.) When he hears Switchblade Sam robbing the house, he goes downstairs and finds George's gold coins missing. He runs outside to tell him just as the flower is beginning to bloom, which causes George and all the guests to miss its entire lifespan. Not knowing about the robbery, George severely scolds Dennis, tells him that he doesn't want to see or know him anymore, and to get out of his way. Shortly thereafter, a tearful Dennis gets on his bicycle (with a wagon attached) and rides off into the night, eventually bumping into Switchblade Sam in the woods. Sam then abducts him, intending to use the child as a hostage.Dennis' parents return home and learn of his departure, and they, the authorities, and his friends (Joey, Margaret, Gunther and all the neighborhood kids) start an intense search. George joins them, as he now feels intense guilt and remorse after remembering all the harsh things he said to Dennis (having now discovered his house was burglarized, and that Dennis actually had good intentions in trying to warn him). Around the same time, Dennis unintentionally but effectively defeats Switchblade Sam by tying him up and handcuffing him (trying to show Sam the only way of tying up Dennis), losing the key (by force feeding it to Sam from a kettle of baked beans), and repeatedly setting him on fire, amongst other things. He returns to George's house the next morning with Switchblade Sam in his wagon, having also recovered George's gold coins, and Sam is taken into police custody by a sheriff who had previously advised him to leave town. The amused sheriff tells Sam, "Now you can tell everybody in the big house you've met our Dennis Mitchell." Dennis and George make up, and the Mitchells and Wilsons become friends on better terms. That night, George explains that he's learned some things about Ryan, Winnie the Pooh, Ash Ketchum, Littlefoot, Spongebob, Skipper, The Fantasy Adventure Team, Bobby, Cindy, Greg, Marcia, Peter, Jan, Oliver, Millicent, DJ, Stephanie, Michelle, Alex, Nicky, Malcolm, Mallory, Reese, Renee, Dewey, Daisy, Emily Yeung, Daniel Cook, the Jungle Adventure Crew, the Madagascar Crew, the cubs, Aladar, Taran, Jesse, Mikey, Bloom, the rest of the characters and children: "Kids are kids, you have to play by their rules, if you can't do that, you're headed for trouble. You have to roll with the punches, and expect the unexpected." While Dennis is making marshmallows, one catches fire. He tries to douse it by rapidly moving the marshmallow stick in the air, but the marshmallow eventually flies off, still burning, and lands on Mr. Wilson's forehead.The film's end credits are accompanied with Dennis inadvertently humiliating his mother's egotistical coworker, Andrea, while she is using a photocopier, which Dennis is sitting by, asking to help. After Andrea says that Dennis doesn't know which button to press, Dennis responds by telling her that he knows which button to press and impishly whacks the "PRINT" button. Andrea loses her balance and her head gets pinned face-down on the scanner-bed, causing Dennis to run away, and the machine relentlessly flashes its blinding light in her eyes as it repeatedly "takes her picture" and spews out page after page of black-and-white "photos" showing her various agonized facial expressions as she writhes about on the scanner bed.
- Bobby, Cindy, Oliver, Greg, Marcia, Peter, Jan, DJ, Stephanie, Michelle, Malcolm, Mallory, Resse, Renee, Dewey, Daisy, Alvin, Simon, Theodore, Brittany, Jeanette, Elanor, Sarah Baker, Jake Baker, Henry Baker, Kim Baker, Jessica Baker, Mark Baker, Mike Baker, Lorraine Baker, Nigel Baker, Kyle Baker, Spanky, Stymie, Froggy, Porky, Buckwheat, Uh-Huh, Waldo, Mary-Ann, Jane, Darla, Alfalfa, Aldo, Ethan, Marissa, Bina, Ely, Otter, Lau, Mick, Naoko, Becky O'Shea & The Little Giants Gang, Tommy, Dil, Chuckie, Phil, Lil, Kimi, Angelica, Susie, Harold, Nicole, Z, Patty, Katie, Robby, Brian, Pepper, Molly, Duffy, Kate, July, Tessie, Vada, Thomas J., Dennis The Menace & Friends, Shake It Up: Camp It Up (Flynn and his friends), Casper, Wendy, Jazmine Payne, Carly Shay, Spencer Shay, Freddie Benson, Sam Puckett, Gibby, Nigel Baker, Kyle Baker, Mike Baker, Mark Baker, Jessica Baker, Kim Baker, Sarah Baker, Jake Baker, Henry Baker, Lorraine Baker, Cooper, Dylan Schenk, Ben Hilton, Jamie, Max, Becca, Nicky, Jeannie, The Flash/Tony, Crispin, Dylan, Duncan, Sean, Tony's Brother, Juel, Erin, Shirley Temple, The Barney & Friends and the Gang, German Speaking Boy, The Chipmunks (Alvin, Simon, and Theodore), The Chipettes (Brittany, Jeanette, and Eleanor), Aldo, Ethan, Miarissa, Bina, Ely, Otter, Tilly, Tom, Tiny, Ramona, Tina, Teddy, Denise, Derek, Harry, Rusty, Walter, Max, Sharkboy, Lavagirl, Linus, Marissa, Ely, Otter, Bindi, Rosie, Kelly, Lynn, Annie, Molly, Pepper, Duffy, Kate, July, The Fraggle Rock Gang, Andy, Ruby, Gracie, Kyle, Chyna Parks, Olive Doyle, Fletcher Quimby, Lexi Reed, Cameron Parks, Nat Wolff, Alex Wolff, Thomas Batuella, Allie DiMeco, David Levi, Qaasim, Cooper Pillot, Jesse Draper, Michael Jackson & Friends, Michael Jackson Badder, Spanky, Stymie, Froggy, Porky, Buckwheat, Uh-Huh, Waldo, Mary-Ann, Jane, Rascals #1, 2, 3, and 4, Friends of Stymie and Uh-huh, Darla, Alfalfa, Little Carbon Soldiers, Becky O'Shea, Junior Floyd, Jake Berman, Rudy Zolteck, Tad Simpson, Hanon, Marcus, Timmy Moore, Nubie, Johnny Vennaro, Briggs, Patterson, Priscilla O'Shea, Murphy, Keith, Marcus, Hector, Jessica, Lisa, Shock, Pete and Pete, Pablo, Tyrone, Tasha, Uniqua, Austin, Paul, The Oslen Twins, Calvin Cambridge, Murph, Ox, Marlon, Reg Stevens, Max Keeble, Megan, Robe, Kevin McCallister, Alex, Leah, Matilda, Penelope, Matthew, Dwayne, Steve, Robert, Nelly K., Sonny, Tawni Hart, Chad Dylan Cooper, Nico Harris, Grady Mitchell, Zora Lancaster, the Baby-Sitters Club gang, Simba, Nala, Timon, Pumbaa, Baloo, Kovu, Kiara, Uncle Max, Ma, Taran, Princess Eilonwy, Fflewddur Fflam, Gurgi, Jesse Greenwood, Elvis, Randolph Johnson, Nadine, The Goonies (Mikey Walsh, Brand Walsh, Mouth Devereaux, Data Wang, Chunk Cohen, Andy Carmichael, Stef Steinbrenner, and Sloth Fratelli), Scooby-Doo, Shaggy Rogers, Fred Jones, Daphne Blake, Velma Dinkley, Yogi Bear, Boo-Boo Bear, Snagglepuss, Huckleberry Hound, Quick Draw McGraw, Augie Doggie and Doggie Daddy, Wally Gator, Magilla Gorilla, Top Cat, Peter Potamus, Woody Woodpecker, Ttark, Toaster, Lampy, Radio, Blanky, Kirby, Fievel Mousekewitz, Tiger, Tony Toponi, Tanya Mousekewitz, Yasha Mousekewitz, Papa Mousekewitz, Mama Mousekewitz, Charlie Barkin, Itchy Itchiford, Hubie, Rocko, Jack Skellington, King Louie, Genie, Louis, Sebastian, Alex, Marty, Melman, Gloria, King Julien, Maurice, Mort, Roger Rabbit, and The Entire LionKingHeart Fantasy Films team and the rest of the characters will guest star in this film.