Eliza May "Liz" Powell is Marge and Herbert Powell's first-born daughter and older sister of CJ, Jacky, and Steph. She enjoys being her parents' little princess for the first five years in her life until her brother CJ was born, and Eliza starts feeling neglected. Despite her egotistical behavior, smug arrogance, and constant complaining she is very popular at school but disliked by her own siblings.

To prove her independence she spends more time with friends than with her family, and befriends teenage children her age who seems to have a bad influence on her. She loves doing bad things for the fun of it, despite the trouble she gets into. Due to her extremely bad behavior, she is sent to an all-girls private school in Waverly Hills, and only sees her family during holidays and family reunions. Even though this was a decision her parents have made for her own good, she blames her siblings for being sent away from home.

But despite her cold and abrasive behavior, Eliza has proven more than once to be the overprotective sister to her younger siblings, stood up for CJ to their parents when he once again got himself in some trouble, got into a fight with her cousins Bradley and Lexie when they accidentally broke Jacky's toy drum set, or even stayed at the hospital to watch over her baby sister Steph when she had the chicken pox.

Eliza starts Elementary in Waverly Hills a year sooner than other children, making it difficult for her to emotionally adapt to her older classmates. She doesn't care much about school and grades, but she doesn't like failing, either. And because of her photographic memory, she passes all exams outstandingly without having ever to study hard.

She is sent to an all-girls private school after blowing up her principal's car just to win a dare. Despite her excellent grades and being a top achiever Eliza never won remarkable awards due to her destructive nature.

At 17, she runs away from home and meets her long lost uncle, Homer Simpson, working in a band, and who, she thinks, "looks just like her dad but cooler". She turns over a new leaf after learning about her uncle's poor lifestyle but still being a caring man who treats her like the daughter he never had. Eliza eventually comes back home where her family welcomes her with open arms.