Meester was born while her mother was serving a federal prison sentence in Fort Worth, Texas. Although her mother, Constance, was serving time in prison for her involvement in a drug ring that smuggled marijuana from Jamaica to the United States, she was able to give birth to Meester in a hospital and nurse her for three months in a halfway house before returning to prison to complete her sentence.
Meester maintained that her parents gave her a normal upbringing and, despite their criminal past, are good people with experience that has only made Meester more open-minded and non-judgmental, "It made me realize that you can't judge anyone—especially your parents—for what they've done in their past, because people change."Meester jokes, "Look, I could've turned out a lot worse."
Meester grew up in Marco Island, Florida, where she participated in productions at a local playhouse. When she was 11 years old, Meester and her mother moved to New York. Meester attended the Professional Children's School and also began working as a model with Wilhemina, booking a Ralph Lauren campaign shot by Bruce Weber and working with then photographer (now film maker) Sofia Coppola. Meester made her television acting debut as a murder victim's friend on an episode of Law & Order. At 14, Meester moved to Los Angeles, California, wanting more stable work and attended Hollywood High School and Beverly Hills High School. She then transferred to a small private school and graduated a year early.
After her television debut in 1999 playing Alyssa Turner in Law & Order, Meester appeared as a guest in two more series before landing her big role in the movie Hangman's Curse, based on the best-selling book by Frank Peretti. Meester also appeared in Tarzan, which ran for only eight episodes. Meester started to land guest roles in other series such as Crossing Jordan, 7th Heaven, Veronica Mars, 24, and Entourage.
In 2005, Meester began a regular role in the series Surface as Savannah Bennet. Meester appeared in two more 2006 movies, Flourish and Inside. She also guest appeared in Numb3rs and in two episodes of House M.D. as Ali, a young girl who has a crush on House.
After guest roles on CSI: Miami, Shark, and playing the female lead in the horror film Drive-Thru, Meester was cast in CW's Gossip Girl as Blair Waldorf. The show is based on the book series by Cecily von Ziegesar about the lives of New York's privileged Upper East Side young adults. Her performance has been met with critical acclaim.
In 2007 Meester appeared on the television film The Haunting of Sorority Row, and played a part in the ensemble comedy/drama Remember the Daze. She also appeared in the horror/thriller film Killer Movie in 2008.
Meester had a small role in the 2010 comedy Date Night. She was cast in Screen Gems's upcoming dramas Country Strong and The Roommate. She will star in The Uncatchable Cowgirl Bandits of Nottingham, Texas alongside Amber Heard. She was cast in indie dramatic comedy The Oranges opposite Hugh Laurie; and will star next to Selena Gomez and Katie Cassidy in young femme comedy Monte Carlo, loosely based on Jules Bass's young-adult book Headhunters.
In June 2009, there were reports accompanied by voyeuristic pictures allegedly from a sex tape, featuring an 18-year old Meester, being shopped around by an old boyfriend for an asking price up to $1 million. Meester counters the allegations in an interview with the September 2009 issue of Harpers Bazaar: "[The tape] is not real, so it makes me sort of sad. It's unfortunate that it got carried as far as it did. I definitely understand the nature of people better now and that the mere allegation of something like that could be headline news. People think it's real because somebody says it is."