Ms. Cantwell was a "permanent" substitute teacher at Lisa's class. She hates blondes believing them all to be stereotypical dimwits who use their looks to get by in life and therefore goes out of her way to be mean to them, including her own 8 year old students. Due to her blonde hair she bullied Lisa.
She punished Lisa harshly for any reason, took every chance to belittle and mock her, and giving her poor grades despite good work. Lisa realized her new teacher was bullying her.
After her father convinced Edna Krabappel to help her, Edna brought in the "nuclear option" to get rid of Ms. Cantwell: Bart Simpson. During a 2-minute bathroom break, Bart managed to trash the classroom and post a video of her in the bathroom, grumbling about how she hates Lisa. The plan worked - Ms. Cantwell quit her job on the spot. Lisa said she could make it stop if Ms. Cantwell would like her, but the woman refused.
As Ms. Cantwell drove away, Lisa pleaded with her to find out why Ms. Cantwell didn't like her. Cantwell's initial reply was that it was something that just happened, but as she continued, she revealed she had a deep seated hatred of 'pretty blonde party girls's who bookworms like her couldn't compete with. She decided Lisa was one such girl because of her blonde hair and the fact she wore pearls despite only being eight.