Megan, aka Megatron "Meg" Harvey Oswald Griffin is the oldest child of Lois and Peter Griffin, and the sister of Chris and Stewie Griffin. She is currently attending James Woods Regional High School. Meg explains in "A Fistful of Meg" that her father changed her birth certificate to "Megatron" after her mother had already selected Megan. Despite this, she is still commonly called Megan such as by Mr. Berler in "Let's Go to the Hop", Stewie in "A Very Special Family Guy Freakin' Christmas" and by Quagmire in "No Giggity, No Doubt". In "Meg's Wedding", Bruce gives her middle names as 'Harvey Oswald'.

Meg is relatively unremarkable in appearance, sporting shoulder-length brown hair, visually short arms, lack of curves and nearly always wearing a beanie-like hat. Most characters on the show always consider her grotesque. She wears the cap under her yellow top hat in the show's opening dance number. She has been seen without her hat on in a handful of episodes for extremely small periods of time. However, in "Untitled Griffin Family History", she is seen without her hat on, as she is in pajamas for most of it. She appears to have inherited the shape of her nose and head from her mother, and her brown hair and myopia from her father.

In "A Picture's Worth a Thousand Bucks", an employee at a carnival guesses her weight as being "a lot". There are several comments aimed at her weight in various episodes, though her girth may be due to her height, as she is the same weight as her mother, making her approximate weight 140 pounds. In "Don't Make Me Over", Stewie has a disturbing thought picturing Meg in low-rider jeans, which shows Meg striking a pose which her belly is exposed up to an inch or two above the belly button, which the fat in her stomach hangs over her waist, resembling a muffin top. Stewie proceeds to beat the thought bubble with a rolling pin. In "Barely Legal", she says she has to buy a new dress to go to the prom with Brian because all her dresses makes her look fat, implying that she is actually fat, not just because of the dresses.

Her plain look is often a topic of humor for the show; characters on the show act as though she were horrifically ugly. In "Mr. Griffin Goes to Washington", a very ugly girl is hired to stand next to Meg so she will look better by comparison. In "Don't Make Me Over", two people drench themselves in gasoline, set themselves on fire, and throw themselves out a window screaming in horror after simply looking at Meg. In another episode, a young man fired a nail gun into his own stomach in order to avoid a date with her. Also, in "Barely Legal", Meg's "backup" date, Jimmy, says he has to attend his little brother's funeral after briefly closing his front door and promptly shooting his little brother. Her "ugliness" may also be a source of her unpopularity. Meg is often mistaken for a boy such as when she asked Craig Hoffman to go out on a date with her in "Don't Make Me Over". She is mistaken for the star of Malcolm in the Middle in "Breaking Out is Hard to Do". There was also when Meg was held hostage by three burglars who mistook her for a boy in "Untitled Griffin Family History". Later in that episode she asked one of the robbers if they were going to "have their way" with her. They refused, disgusted by her appearance and she got angry, shouting at them to have sex with her and insisting she was 'pretty'. They then filed a sexual harassment suit against her, which went ignored by Peter, who thought she was going to a dance, leading to her arrest. Peter also passed her off as a boy named "Greg" in "Big Man on Hippocampus" to qualify for Family Feud. In "Quagmire's Dad", Ida Quagmire believed that Meg also got a sex change operation to become a girl like he did. In "Prick Up Your Ears", Meg took an abstinence vow with her new boyfriend up until the end of the episode, where after seeing her nude, he dumped her. Another brief boyfriend of hers, nudist Jeff Campbell had no objections to her looks at all. In "Long John Peter", Chris lifts Meg's top up, exposing her bra, as a means to make Brian throw up as an excuse to take him to the vet. Also, her appearance is displayed as ugly in alternate dimensions, where even her sexy version was still considered ugly by the dimensions standards in "Road to the Multiverse".

Meg received a makeover in "Don't Make Me Over", drastically increasing her sexual appeal in the eyes of characters in the show after several people in the episode covered themselves in petrol and burned themselves. It was during this brief period when Meg, a popular singer at the time, lost her virginity to Saturday Night Live comedian Jimmy Fallon as part of an elaborate cold open sketch. In "No Chris Left Behind", She participates with Lois in prostitution in order to pay for Chris' school, Lois gets picked up and Meg is left behind. In "Quagmire and Meg", Meg rarely has eyebrows when she is seen without her glasses.