On The Simpsons, the only subject Lisa has ever failed is gym. The detail is central to the Season 6 episode “Lisa on Ice,” in which Lisa discovers that her perfect academic record has one embarrassing exception: physical education.
Lisa is portrayed as exceptionally intelligent, conscientious, and academically driven. Her failure in gym is therefore funny precisely because it clashes with her usual identity. She struggles with athletic exercises and is mortified that a subject requiring physical performance can threaten her otherwise spotless school record.
The episode turns that setup into a larger story when Lisa joins a hockey team. Her competitive rivalry with Bart initially threatens their relationship, but the siblings eventually set aside the contest and play together. The episode is remembered both for its sports plot and for revealing Lisa's unusual weakness.
Viewers sometimes confuse this with Lisa failing a particular test or assignment, since the series occasionally shows her bending rules or making mistakes. The trivia refers to a school subject, and the canonical answer is gym, also called physical education.