While watching Eye on Springfield on TV, Homer and Marge see an advertisement for a gala at the South Street Squidport. Upstairs, Lisa and Janey are reading through their series of The Babysitters Club books. This inspires Lisa to want to begin babysitting. She places an ad with Reverend Lovejoy at church, but she has no takers.
Lisa is disappointed with no one willing to trust her to watch their offspring. But when Ned Flanders comes over to ask Homer to watch Rod and Todd in order to pick up Maude and her mother, Homer can't think of an excuse not to. Lisa jumps at the idea, but Flanders is hesitant. Finally, with few other options, he gives Lisa her first babysitting job. In the process, Lisa watches Rod and Todd and learns that they are very fragile children. She dreads their junior high life...
Her success means Lisa continues to get more jobs. Soon, Bart notices that Homer and Marge come downstairs to attend the gala down at the South Street Squidport. It doesn't sit well with him that Grandpa isn't going to be babysitting; that would mean either Patty or Selma is coming. But Marge tells him, to a great injustice and understandable outrage, that he and Maggie are being babysat by his little sister Lisa.
While Homer and Marge attend the gala, Lisa tries to get Bart to warm up to her, but it does not work. He begins the mayhem at the table, where Lisa tells him that he should stop being a baby if he doesn't want to be babysat. Bart takes this to an extreme and starts acts like a baby, which starts upsetting Maggie. Bart figures he'll get her to quiet down by giving her some ice cream. This creates another problem; Maggie starts to get hyper. Lisa tells Bart that was coffee ice cream and he had just caffeinated Maggie.
While Lisa tries to fetch Maggie off the shower curtain rod, Bart starts to make a series of phone calls. Once she grabs Maggie, she is sick of Bart and ends up having to drag him up to bed. At this time, the doorbell rings. Lisa answers the door to find sub sandwich delivery men, Krusty showing up for a bachelor party, an emergency response team, a government agent and a chauffeur for the Ambassador of Ghana. Furious with the fact it was all a big trick, Lisa forces them out of the house. Fed up with all the trouble he's caused, Lisa tells Bart to go to bed, but he uses this as a further reason to drive her up the wall. He avoids her attempts to grab hold of him which ends in Bart falling down the stairs, resulting in a serious injury.
Bart now has a large lump on his head and a dislocated shoulder. Lisa urges him to let her try to relocate it but Bart refuses, wanting to use it as more evidence to damage Lisa's reputation. Bart soon locks himself in his room with Lisa pleading him to open the door with drastic promises. At this time, Bart starts banging his head against the door, trying to make the lump on his head bigger. Lisa orders him to stop, but the only response she gets is a thud. Worried by the sudden silence, Lisa crawls from a window to a tree branch to find Bart is now unconscious.
Lisa calls 911, but they refuse to take her call seriously for the earlier call. Worried that Dr. Hibbert might think Bart's injuries were a result of bad babysitting, Lisa decides against it to see Dr. Nick. She loads Bart into a wheelbarrow, nervously trying to convince herself that everything will be fine. But when Maggie starts to get restless, Lisa throws her inside a cat carrier hoping it will settle her down. The line to Dr. Nick's clinic is too long and Lisa must walk a long distance to the nearest hospital. Lisa is soon stopped by Chief Wiggum, and she tries to hide the unconscious Bart and Maggie in a cage. Chief Wiggum remains oblivious and leaves. Lisa finds Bart is no longer in the wheelbarrow and is tumbling down into a mud puddle. Lisa follows him down the hill, thinking the whole evening was a nightmare. It gets worse when she is found right next to the South Street Squidport. Everyone thinks Lisa has killed Bart and intends to dispose of the evidence, and drown Maggie with him.
The next day, Bart, with his arm in a cast, goes to apologize to Lisa. When she answers the phone, she is able to have more babysitting offers come in.