When Marge bumps her head on a stool by her maximum-strength cleaning solution she uses to clear the house before her free housecleaning (which "she" won thanks to Homer painting the address number on the curb in front of the house), she gets amnesia, but quickly remembers everything except for two things - one, that she's married to Homer, and two, who Homer is.
Looking for a way to get easy money, Bart, Milhouse, and Nelson go around town spray-painting people's addresses on their curbs and make them pay them ten dollars, and when Ned Flanders pay them and ask them to paint his garage for $100, they freak out. After they already add the "7" and the "4" to the Simpsons' curb, Homer tells them that he won't pay, so they leave without finishing. The next day, the letter carrier delivers them someone Else's mail, thinking that their address is 74 Evergreen Terrace. Homer continues to accept the mail. One day, Marge gets a letter claiming that she has won a contest from a magazine she doesn't even subscribe to. Nonetheless, her prize is that a maid will clean the house for a day while she relaxes. Highly afraid the maid will be mad if the house is dirty, she cleans everything, from vacuuming the air ducts to dusting a key hole. When the house is entirely spotless, Marge thinks the house is ready to be cleaned, but the only thing in the entire house that is dirty is a tiny spot. Still afraid the maid will scold her she panics wanting the entire house to be 100% clean. She combines all of her different cleaners together, but the fumes make her woozy. She falls and hits her head on a stool. When she wakes up in the hospital, it is revealed that she has amnesia and can't even remember her own family.
After failing to jog her memory, the family returns home. However, when Marge hears Maggie suck on her pacifier, she suddenly remembers her. Then, when Lisa uses a slew of fancy words, Marge then remembers her. And then, when Milhouse comes in to tell Bart that he's now lactose tolerant, she remembers both Bart and Milhouse. Despite remembering Ned's cat's birthday, she cannot remember Homer.
Homer tries to get her to remember him, but to no avail. He then attempts to try to make Marge fall in love with him again, but he only makes her disgusted in him, as she selfishly says that the greatest thing that's ever happened to her was forgetting about him. She kicks him out of the house. Patty and Selma excitedly take Marge to a speed date, and she meets a man who shares her same interests. But when Marge tells him that she has amnesia and three kids, but he rejects her and leaves her. Homer catches up with him and scolds him for leaving her, saying that she is the most beautiful and kind woman he'll ever meet. Still, he leaves. Marge then tells Homer that even though she may not remember him, he knows the most wonderful things about her. As they drive back home, Homer brings up beer, and she suddenly remembers him. The episode finishes with Homer driving (drunk, apparently) into the sunset. During the credits, Homer is asking Marge if she knows any of the people listed.