Meg is a self-conscious teenage girl. Her self-consciousness causes her to desperately try to be part of the cool crowd, but this only results in her getting coldly rebuffed by Connie D'Amico,[2] an insensitive, egotistical and irresponsible cheerleader. However, another student named Neil Goldman is attracted to her.[3] She is also usually at the bottom of the family's pecking order and the butt of Peter's jokes due to her homeliness, tendency toward social awkwardness and lack of popularity. Everyone in her family, especially Peter and Chris, makes fun of her in every possible way they can. She has been so self-conscious and insecure about herself that she has engaged in dangerous sexual behavior just for attention.

Meg desperately tries to be part of the cool crowd, but is usually coldly rebuffed. She is also usually the butt of Peter's jokes due to her homeliness and tendency towards social awkwardness. Because of her eagerness for acceptance, she has been recruited unknowingly into a suicidal religious cult,[11] and, later, recruited, again unwittingly, into her school's Lesbian Alliance ("Brian Sings and Swings").[12] However, in some episodes, Meg is seen with a group of girls who are attending her slumber party and gossiping about boys.[13] In later episodes, these girls are characterized as being highly unpopular and dateless, much like Meg, even saying that she was the only one of them who ever had a boyfriend (actually a decaying corpse she was "dating").

She is so unpopular in high school that one student fires a nail gun into his own stomach twice (in shop class) in order to avoid a date with her, and then in a later episode shoots his own brother to have an excuse not to go to a dance with her the following night. On another occasion, Meg and Lois are looking for new clothes for Meg, but with no luck. They hear about the Channel 5 News contest for people giving out makeovers after two people ended up pouring gasoline on themselves, lighting a match, catching fire, and then jumping out of a window. However, she is sought by nerd Neil Goldman. In 8 Simple Rules For Buying My Teenage Daughter, Neil starts dating a girl named Cecilia, Meg becomes instantly jealous and pretends to date Jake Tucker to make him jealous. This leads to her signing a contract to become Neil's girlfriend and (not knowing at first) his slave, but she gets him to tear up the contract after Lois seduces him. Perverted neighbor Glenn Quagmire has shown a repeated interest in her, mostly due to his very low standard, asking if she has reached the age of consent (which would be 16 in Rhode Island, but he always asks if she is 18, which is what many people assume is the nation-wide age of consent).[14] In several episodes she is shown dating, including stories with characters Mayor Adam West[15] and nudist Jeff Campbell.[16] She also loses her virginity on live television to Saturday Night Live host Jimmy Fallon after having a drastic makeover; but, before all that happens, she goes out with a rebel at her school named Craig Hoffman.

Though Meg was no different than any other member of the family in the first two seasons of the show, this began to change as MacFarlane started to flesh out the characters to the point where it seems that most of the population of Quahog, including her own family, despise her for no reason other than her simply being "Meg". Meg is the oldest child in the Griffin family, and the most misunderstood, at least by Peter, Chris, and others who are shown avoiding her company, disparaging her in person, gathering in her bedroom to read her diary for laughs, Peter reminds Lois "We agreed that if we could only save two, we'd leave Meg!" even randomly shooting her when she simply said "Hi Dad" ("Peter's Daughter") but despite this he also was going to say "I love you" in "Hell Comes to Quahog", and in "Road to Rupert" he stated they were 'secret best friends' before throwing lemonade in her face, saying he would have to continue to treat her badly in public in order to maintain his reputation due to "peer pressure", thus giving hope that they may be on good terms. Occasionally, when Meg asks a question to Peter or just speaks when he is in the room, Peter responds by saying "Shut up, Meg"-immediately followed by a line from another character.