Portrayed by Blake Lively in the TV series, Serena van der Woodsen is described as a stunning, ethereal 5'7" beauty, having blond hair and navy blue eyes. Many of the gossip girls at Constance Billard envy her, giving her beauty perfect credits for everything Serena achieved in her life. She is smart, but often people judge her on looks alone. Those who don't judge her by looks, tell her that she's not working at her full potential. Serena van der Woodsen is charming, calm and, of course, the "talk of Manhattan". Her parents are on the boards of all major charities and art organizations in the city. Despite the attention she receives from the opposite sex, Serena van der Woodsen longs for true romance, which she tries to find in Dan Humphrey.

When Serena van der Woodsen unexpectedly returns to New York under a cloud of suspicion, she is initially unwelcome by her best friend Blair Waldorf, who is upset by the lack of contact during Serena's absence, and has assumed the position as 'queen bee' of Manhattan's social scene. After she returns, Serena van der Woodsen is focused on changing and becoming a better person, unlike in the books with the same name, where she's still going to gossip girls parties and wanting things return to normal.

Having discovered that her boyfriend Nate slept with Serena van der Woodsen a year before, Blair is unwilling to continue their friendship. After the affair, Serene felt the need to escape to boarding school, but had to return a year later, because she was kicked out for returning late in the beginning of the school year. Serena van der Woodsen also left for another reason: a guy she was with overdosed on drugs and died, while her 'good' friend Georgina filmed the whole scene on tape.

Back in Manhattan, Serena van der Woodsen meets the outsider Dan Humphrey and begins a relationship with him. At the same time Dan's father Rufus and Serena's mother Lily revive their past relationship. Because of Blair's wrongful public defamation of Serena van der Woodsen and the realization that Serena's brother had attempted suicide and was secretly receiving treatment, Blair tries to mend their gossip girls friendship.

Serena van der Woodsen mixes lots of fashion-forward and vintage pieces together for a look that is 'boho chic' with a rocker-chick edge. (See Links you'll Love for more details)

Throughout the year, Serena van der Woodsen and Dan's relationship is continually tested by the elite class, the other gossip girls and the return of his best friend Vanessa. Yet, despite such problematic situations, their relationship grows stronger by each week. However, the closing of junior year is accompanied by Serena and Dan's relationship beginning to erode. While they attempt to fix it, Dan is unable to cope with the lies and class differences that separate him from Serena van der Woodsen; therefore Dan and Serena break up at the Bass wedding.