Conrad and Sally Walden live in the town of Anville with their single mother Joan, who works for neat-freak Hank Humberfloob as a real estate agent and is dating next-door neighbor Lawrence “Larry” Quinn. Joan is scheduled to host an office party that evening at her house, whereupon she forbids her children from entering the living room which is being kept pristine for the party, which would result in her dismissal if it becomes messy. When Humberfloob asks Joan to come back to the office, she leaves her kids with lethargic babysitter Mrs. Kwan.
After Mrs. Kwan falls asleep, Conrad and Sally encounter the Cat in the Hat, an oversized, anthropomorphic humanoid talking cat with a red-and-white striped top hat and red bow tie who expresses a desire to teach them about having fun. In his presence, the Cat releases two troublemaking creatures, named Things 1 and 2, from a crate and they leave a trail of destruction throughout the house as the Things only do the opposite of what they are instructed.
After witnessing Conrad open the crate, the Cat tells Conrad not to open the crate as it is a portal to his world. Despite the Cat’s warning, Conrad picks the lock on the crate, which grabs on to Nevins’ collar as the Things throw Nevins out the window. While the Things stay behind and continue to trash the house, the trio go outside to retrieve Nevins and the lock.