Serena is described as 5 feet 8 inches (173 cm) tall, with huge dark blue eyes and messy long blonde hair. Many of the girls at Constance Billard accuse her of using her good looks as a means to secure that everything goes her way. She is not particularly academically skilled, but she is often told that she is not meeting her full potential. Her father runs the same Dutch shipping firm his great-great-grandfather founded in the 18th century, and her mother, Lillian van der Woodsen, is a socialite. Her parents are on the boards of all major charities and art organizations in the city. The van der Woodsens reside at 994 Fifth Avenue, a ritzy, white-gloved doorman building directly across the street from The Met and Central Park. Serena and her family own half the top floor in a 14 room penthouse.
Serena is often seen as a threat to the other girls as she is mysterious and beautiful. Serena has a nail-biting habit and also cuts her split ends off herself, mainly during her classes at Constance Billard. Though exposed and aware of the on-goings in the fashion world, Serena, unlike Blair, is not as meticulous about her fashion choices and wardrobe. She is described to have an effortless way about her. Serena is charismatic, charming, talented, funny, kind, care free and laid back. These attributes help Serena to thrive and often attract men.
In the first novel of the series, Serena returns to Manhatten where she used to live at the exclusive Constance Billard School for Girls. Before leaving she was best friends with Blair Waldorf. Upon returning, she interrupts a passionate moment between Blair and Nate, and becomes the target of Blair's hatred as she constantly tries to steal the spotlight from Blair. During the series, Serena becomes briefly involved with Dan Humphrey and Blair's stepbrother Aaron Rose.
The Pilot introduces Serena as the wealthy daughter of divorced parents, with a younger brother named Eric. She grew up with her best friend Blair Waldorf and Blair's longtime boyfriend Nate Archibald. Serena returns from boarding school, and visiting Eric at the Ostroff Center, a mental health facility, when he attempted to commit suicide prior to her return and the main reason why she came back to New York. She arrives at a party held by Blair 's mother, Eleanor Waldorf, immediately leaving after seeing a resentful Blair , Nate and her mother, her visit then confirms to Blair and her peers that she has officially returned. Blair ostracizes Serena by denying her an invitation to the Kiss on the Lips party. Serena successfully attempts at reconciliation when she invites Blair to drink with her at the Palace Hotel, patching up old issues such as Serena leaving without saying goodbye and not being there for Blair at the time of her father's divorce. After reconciling, Blair leaves and Chuck arrives, attempting to woo Serena. Chuck reveals that he knows the details of Serena's return, where the audience sees a flash back of a drunk Serena taking Nate's virginity during a wedding, and Chuck attempts to rape her. Serena manages to escape and accidentally runs into Dan Humphrey, a St. Jude's student from Brooklyn, who often expresses cynicism about the lifestyle his wealthier classmates lead but finds Serena a refreshing view of the Upper East side. The following morning, Dan invites Serena to a date as Serena shows reluctance at attending the Kiss on the Lips party. Their date goes smoothly but ends with them attending the party trying to save Jenny Humphrey, his little sister, from Chuck 's unwelcome advances. Serena leaves with Dan but not without noticing Blair 's hostility but that Blair has discovered her incident with Nate .
The day after the Kiss on the Lips party, Serena's growing romance with Dan and her friendship with Blair becomes severely strained when Serena discovers that Blair had discovered her incident with Nate. Dan sets a date with her their date is dragged into another Upper East side event with Chuck's father holding a brunch. Nate attempts at reconciling Blair and Serena but the attempt sets Blair into sabotaging Serena's romance with Dan, telling him about Serena's incident with Nate and further implying that she is no different from her Upper East peers. Dan ends his date with Serena and leaves her. Serena is then seen looking at past photos of Blair and her friends on her phone and then dumping her phone into a trash can.
Ivy Week sets Serena and Blair at each others' throats as they sabotage each other. When Blair threatens Serena about her secret concerning her visits at the Ostroff center, Serena comes up in front of the audience at Ivy Week, becoming the scapegoat at Blair's attempt at humiliating her, potentially ruining her chances at college. Eric eventually confronts Blair, who feels guilty and apologizes to Serena at the events of Ivy Week. The two form an uneasy truce as Serena reveals her own guilt at what she did to Blair and Blair expresses her anger at Serena for her abrupt leave at her time of need.
The truce is short-lived as Blair's insecurities about her mother's seeming preference for Serena arises, especially when Blair's mother Eleanor Waldorf chooses her as fashion line's model instead of Blair. Blair becomes frustrated and Serena confronts her about her fears over Serena taking over her life. Dan eventually sets things right with Blair and both Serena and Blair reconcile.
Serena relationship with Dan eventually blossoms after the issue of trust is tested when Vanessa returns from Vermont and during Blair's seventeenth birthday party. Serena and Dan then concern their relationship becoming a sexual relationship but the two do not go forward at having sex as Serena reveals that she neither remembers the man she lost her virginity to nor does she remember his face and Dan then retracts back to his stance on the nature of sex.
Serena soon discovers her mother, Lillian van der Woodsen's past relationship with Dan's father Rufus Humphrey during Thanksgiving. At first the discovery threatens her relationship with Dan but she later concedes to her mother's past, and both she and Eric get to know their mother better.
Her relationship with Dan is once again tested when her maternal grandmother CeCe Rhodes aids in holding her Cotillion. CeCe refuses to acknowledge Dan as Serena's boyfriend and does her best to strain Dan and Serena's relationship. Dan reveals CeCe's manipulative nature to Serena before Cotillion and Serena chooses to go with Carter Baizen, her grandmother's suggested escort to her Cotillion who also has past history with her in Santorini. Dan and arrives and proves his love of Serena, impressing CeCe and sweeping Serena off her feet during Cotillion.
Serena spends the Holidays with the Bass family and has trouble finding a gift for Dan as she learns that she should get to know Dan better. Vanessa aids her throughout her gift giving scenario and when the two exchange gifts, she gives Dan a present of snow and a winter wonderland, receives her present of reading Dan's first story, and the two have sex. Meanwhile, Serena's mother, Lillian van der Woodsen, notorious for her many divorces, becomes engaged to Bartholomew Bass, Chuck's father.
A pregnancy scare occurs when Serena is spotted buying pregnancy test, one that she took a public bullet for as she bought it at Blair's request. Her reaction to Dan's "I love you." is mixed and has her frustrated at him, knowing that he said it because of the pregnancy scare. She and Blair however have another fight over the pregnancy scare. Dan has trouble saying "I love you." to Serena but later has the courage to do so, citing the reasons why he loves her. Serena leaves to continuing do one of those reasons and helps Blair throughout her ordeal when she intends to leave the Upper East side for a semester in France after she is humiliated.
Serena and her family eventually move in to Bart Bass' penthouse suite. Trouble brews as Serena eventually gets Chuck kicked out of their apartment because she assumes that the narcotics and pornography being sent to her are from him. However, it turns out these gifts are from an old friend, Georgina Sparks, a party girl from Serena's past who intends to return to Manhattan.
Georgina's return brings back touches of the old party-girl Serena. But Serena being wiser since her return, rejects Georgina and finally confronts her after she missed the SATs followed by a series of events that lead to her lying to Dan. Georgina sends another gift as she views a video of what seems to be a sex tape and imposes herself into Serena's life posing as "Sarah". Georgina pretends to be a girl named "Sarah", and manipulates Dan into being suspicious of Serena. Georgina first uses the supposed sex tape to blackmail her into retracting back to her party-girl self.
Georgina blackmails Serena by threatening to tell Dan why she left for boarding school. Dan then confronts Serena and asks her what is wrong, and she tells him that she cheated on him. This is a lie, but her rationale being that she would rather have Dan think she cheated on him than him know what she actually did. It is then revealed that the real reason she left so suddenly for boarding school was that after she slept with Nate, she and Georgina snorted cocaine with a boy named Pete and he tried to have sex with her. He overdosed on cocaine and she and Georgina ran from the hotel room. Serena then ran away to boarding school having learned that Pete Fairman died as the police took him out of the hotel they had stayed in in a body bag.
When Serena attempts to find Dan and explain to him everything that had happened during a concert, she gets a call from Dan only to hear a reply from Georgina implying she'll have sex with Dan and turns off Dan's phone. Serena spends the night trying to call Dan .
The first season finale has Serena going to the Humphrey loft the next morning and is relieved to find Dan but spots Georgina. She confronts her and lashes out as Dan restrains her from attacking Georgina, who then left. Serena explained to Dan all the past events that had occurred from her real reason for leaving boarding school to Georgina blackmailing her. Dan then brings up her lie about cheating on her with two random men and she explains her rationale being that cheating on him would've been easier to forgive. Dan ends their relationship and the two have one last dance at Lily's wedding to Bart. Serena spends the first two weeks of her summer reflecting.