Blair Waldorf (Leighton Meester) is the daughter of Eleanor Waldorf (Margaret Colin) and the Upper East Side's "Queen Bee". She is best friends with Serena Van Der Woodsen (Blake Lively) and is dating Nate Archibald (Chace Crawford). Blair also befriends Chuck Bass (Ed Westwick) who becomes her partner in several schemes.
After Serena returns from boarding school, Blair finds out from Nate that he and Serena had slept together. Blair displaces her anger by publicly humiliating Serena and revealing to everybody about her trip to the rehab hospital. Later she learns that the reason for her visit was to meet a patient who was actually Serena's younger brother Eric Van Der Woodsen (Connor Paolo).
Blair sleeps with Chuck Bass after she learns that Nate no longer loves her. She eventually falls in love with Chuck, which evolves into a heated love triangle. Blair struggles to keep her power when Jenny Humphrey (Taylor Momsen) comes along. After she unites with Chuck and Nate to save Serena from the scheming Georgina Sparks (Michelle Trachtenberg), Chuck realizes that his feelings for Blair are real and proposes that they spend the summer in Tuscany together.
Blair and Chuck have a continuous love-hate relationship. When Chuck finds out his father is dead, he turns to Blair for comfort. Surprisingly, Blair forms an unexpected friendship with Jenny. While taking a trip to Yale, Blair and Serena make up and apologize for the ill feelings they had before. Yale meant everything to Blair and she was mortified when she found that she wasn't accepted. After a turn of events, Chuck finally declares his love for Blair and the two begin a committed relationship. As always, the relationship doesn't end well.
Blair is surprised when she finds out that Chuck has finally moved on a new woman; Eva (Clemence Poesy). Emotionally hurt and slightly jealous, she tries to sabotage their relationship. It works and Eva eventually leaves Chuck. Blair and Chuck become antagonistic for a short period, but resume their sexual relations again and recognize their love for one another. They break up once more, but this time the break up is a mutual agreement. Chuck promises Blair that he will wait for her and both agree that their love is strong enough to reunite them again in the end.
Blair's best friend Serena, is constantly bothered by Juliet Sharp (Katie Cassidy), the new girl on the Upper East Side. Juliet is out for revenge and Blair doesn't like it one bit, so she and Dan Humphrey (Penn Badgley) team up to find Juliet Sharp in Connecticut, only to end up getting stuck together over the holidays. Their search leads to the uncovering of the dirty truth that had been hidden from everyone by Lily Bass Humphrey (Kelly Rutherford).
"Guess I must have some undiagnosed brain injury. 'Cause I stupidly thought that this fake friendship might be real."
"And I know how to staple, so stay out of my way or I'll use one to attach your tongue to your shoulder blade."