Jean Walden (KELLY PRESTON) is a realtor who works for the "germophobic" Mr. Humberfloob (SEAN HAYES). When it's announced that a party will be held at her house, Jean panics. That's because her boss will fire her if her place is unkempt. She also knows that her son, Conrad (SPENCER BRESLIN) -- despite the best intentions of his fastidious and orderly sister, Sally (DAKOTA FANNING) -- will inevitably make the place a mess.
Thus, she panics when Humberfloob calls her back into work as she's trying to get their home ready. After briefly chatting with her boyfriend, next-door neighbor Lawrence Quinn (ALEC BALDWIN) who wants to send Conrad to military school, she gets Mrs. Kwan (AMY HILL) to baby-sit.
When the perpetually sleepy Kwan doses off, the kids hear a noise in the closet and are shocked to discover a 6-foot tall, talking feline known as The Cat in the Hat (MIKE MYERS). He doesn't think they're any fun and thus wants them to sign a contract where they can have all of the fun they want without getting into any trouble.
Conrad is ready to sign on the dotted line, but Sally - along with the now talkative pet Fish (voice of SEAN HAYES) - think that's not a good idea, but the Cat convinces her. Soon mischievous twins
Thing 1 and Thing 2 arrive and things rapidly spiral out of control.
With the house a mess and the pet dog gone, Sally and Conrad do what they can to clean things up, get the dog back and avoid Lawrence, all before their mom gets home and The Cat and the two Things progressively make things worse.