|“||Nate, I'm really sorry I left the morning after. I never meant to hurt you. I wish that somehow we could relive that night, because this time I'd know that you love me. And you know that I love you.||”|
— Serena to Nate, The Sixteen Year Old Virgin
Before Serena leaves for boarding school, Nate lost his virginity to her; despite the fact that Nate is dating her best friend, Blair Waldorf. Nate chooses Blair at first, but then Serena. In the end, he ends up with neither as he doesn't want to get in between the two girls.
During Pilot, Nate hopes to give a romantic relationship with Serena a real chance when she returns from boarding school. However, Serena refuses, not wanting to hurt Blair anymore than she already has. Before sleeping with Blair for the first time, he tells her that he had sex with Serena. She eventually decides to forgive Nate but orders him not to talk to Serena again. In The Wild Brunch, Nate goes to see Serena at The Palace Hotel where she is living temporarily with her mother, Lily van der Woodsen. While there, he runs into Serena's new love interest, Dan Humphrey. At Bart Bass' annual brunch for his foundation, he asks Serena if they can have a private moment to talk. However, Blair is determined to have sex with Nate and happily obliges when Chuck Bass gives her a key to his suite to do it; not knowing Nate is planning to meet with Serena up there. When he arrives with Blair, she discovers he was planning to meet with Serena and angrily tells Dan what happened. Later that day, he agrees not to talk to Serena again to stay with Blair.
In The Blair Bitch Project, Nate goes to Dan when his sister, Jenny Humphrey, asks for an odd favor. He accidentally interrupts a date between Serena and Dan to ask for his help, then stays with Serena to catch up. In Woman on the Verge, he works with Blair and Chuck to help Serena move on from a traumatic evening with Georgina Sparks. In the season finale, Much 'I Do' About Nothing, he and Serena plan to hang out over the summer as they'll both be in the Hamptons.
In the season premiere Summer Kind of Wonderful, it's revealed that Nate and Serena have spent the summer pretending to date so she can move on from Dan and Nate can have an affair with the married Catherine Beaton. During The White Party, Serena kisses Nate to help him make Catherine jealous, and it works.
In Enough About Eve, Serena goes to Nate for help in freeing her boyfriend, Carter Baizen, from the Buckley family; who are planning to send him to an oil rig as revenge for him abandoning his wedding to Beth Buckley. Nate sets them up to play a game of poker with PJ Buckley, Beth's brother, and convince them to play Carter's sentence. To gain trust with the group, Nate offers to give them a photo of his Congressman cousin, Tripp van der Bilt, smoking marijuana at his bachelor party in exchange for them playing Carter's hand. However, PJ wins the pool and Nate is forced to hand over the photo. Later that day, Serena overhears Nate tell his grandfather, William van der Bilt, that their plan went perfectly. When she confronts him about it, Nate confesses that he knew they would lose the game and when they did, they were going to release the real photo of Tripp so the Buckley's would look like they faked the photo. Angry that she was used, Serena calls PJ to inform him and get Carter his freedom.
In The Grandfather: Part II, Serena starts becoming closer to Tripp and eventually begins an affair with him in The Last Days of Disco Stick. Meanwhile, Nate has realized that he still has feelings for Serena but doesn't act on them when he sees her become involved with Tripp. During Thanksgiving, he obtains a video of Serena and Tripp in the elevator at The Empire Hotel and shows it to Tripp's wife, Maureen van der Bilt. They both confront the two over it, and Lily overhears. She orders Serena to end the affair or be kicked out of her apartment, but Serena chooses to leave when she finds a letter from her father that Lily hid. On her way out, Nate tries to stop Serena by confessing his feelings but she leaves anyway (The Treasure of Serena Madre). The next day, she discovers that Tripp was lying to her and forces him to drive her back to the city. On the way back, they get into a car accident and upon discovering her head injury, Tripp abandons the scene. Nate, who has figured out Tripp was lying to Serena, happens upon the scene and follows Serena to the hospital. He sees Tripp there and punches him in the face before telling him not to go near Serena again. Afterwards, he stays with Serena at the hospital all night (The Debarted).
When Serena is released from the hospital, she and Nate begin to have a romantic relationship. However, both are advised to take things slow and Nate does so by inviting then disinviting Serena from a dinner with the French ambassador. Upset at this, Serena attends with an old friend, Damien Dalgaard, but ends up hooking up with Nate at the dinner. After this, they become official (The Hurt Locket). In Inglourious Bassterds, Serena plans a special surprise birthday party from Nate, but Jenny tries to undermine efforts, as she is harboring a major crush on Nate. During the party, she kisses Nate, who is stunned; then tells her that he's with Serena and has no interest. Later that night, he and Serena spend the night together. Soon after, Chuck offers to throw a wedding for Dorota Kishlovsky and Vanya. Meanwhile, Serena secretly meets with Carter; which Nate discovers only after he finds a key to Carter's hotel room in her purse. He confronts her about it, but she brushes it off, promising it means nothing. Right before the wedding, Carter tells Serena that he knows where her father is and they can go that night if he leaves with her then. Serena chooses to leave with Carter but kicks him out of the car when she learns he lied about when he knew her father's location. On the way to the airport, she tries to call Nate but is only able to get Jenny on the line. She asks her to pass along a message to Nate but she doesn't, as she wants Nate for herself (The Unblairable Lightness of Being).
When Serena returns in Dr. Estrangeloved, she finds Nate is not at all happy at being abandoned. After they spend a day arguing, Nate goes with Jenny and Chuck to an art party in Brooklyn. After they argue briefly on the phone, Nate goes back to The Empire with Jenny, who tells him that he deserves better than Serena. She tries to kiss him, but Nate pushes her away. Unbeknownst to them, Serena entered the room and witnessed the whole thing. She explains to Nate that she tried to call him and that Jenny clearly didn't pass on the message. Nate then kicks Jenny out of the suite to talk to Serena, who tells him that Lily has cancer and her father, William van der Woodsen, is back in town. This reunites the two, who begin to be happy with each other again. Nate encourages Serena to spend time with her mom and suggests she move back home to support Lily. Serena originally decides not to, but changes her mind when she butts heads with Jenny. That night, Serena learns from her neighbor, Holland Kemble, that Rufus cheated on Lily with her (It's a Dad, Dad, Dad, Dad World). As a result, Serena begins to ice Rufus out from the family and the secret eventually comes out to everyone. However, Nate, Dan, Blair, Chuck, and Jenny all agree that there is no way Rufus would ever cheat on Lily. They work together to expose William and Holland's plan, which they're able to figure out. Nate calls a high ranking police investigator to arrest William for prescribing Lily medication she didn't need for cancer she no longer had. When Serena finds out that Nate called to have her father arrested, she distances herself from him and begins to lean on Dan (Ex-Husbands and Wives).
In the season finale Last Tango, Then Paris, Jenny finds Serena and Dan sleeping in his bed together at the loft. She takes a photo and sends it to Gossip Girl, who posts it. Serena heads to The Empire to explain to Nate that nothing happened, then blames him for calling the cops on William. Later that day, Dorota goes into labor and everyone gathers at the hospital. While there, Serena and Dan discuss their one kiss that they shared the night before and Nate overhears. Afterwards, he sends a copy of the GG blast to Vanessa, who is away in Haiti for an internship. That night, Serena breaks up with Nate; saying she needs to be alone for awhile to figure things out.
When the season begins in Belles de Jour, Serena is still trying to choose whether she wants to be with Nate or Dan. Meanwhile, Nate has begun a friendship with Juliet Sharp, a Columbia student who has a mysterious vendetta against Serena. When Serena returns to New York, she learns that neither Nate or Dan is single, so the choice between the two was made for her (Double Identity). When school starts, Serena tries to be friendly towards Nate but he's cold toward her; saying that he didn't realize until now how mad he is at her for dumping him and fleeing town. At Fashion's Night Out, Serena and Blair expose Juliet for sabotaging Serena's entry into Hamilton House. However, Nate sides with Juliet and stops talking to Serena (The Undergraduates).
In Easy J, Nate and Juliet break up and Nate realizes she is the one who fueled his anger toward Serena. They begin hanging out again, and Serena asks Nate to act as a buffer for her at Blair's birthday party so she won't flirt with her professor crush, Colin Forrester (War at the Roses). However, Serena breaks it off with Colin soon after. Afterwards, she calls Dan to say she wants to talk to him about things and offers to wait for him for as long as he wants. However, Nate appears right after and confesses that he still has feelings for her and wants to get back together. Dan then arrives at the scene and Serena disappears upstairs to avoid choosing between the two (Juliet Doesn't Live Here Anymore). In The Witches of Bushwick, Eric and Eliot Garfield create a venn diagram of Nate and Dan to help Serena decide. Meanwhile, Juliet teams with Vanessa and Juliet to ruin Serena's life. Jenny is able to swipe Serena's cell phone SIM card and is able to send messages as her. Meanwhile, Nate and Dan agree to each invite Serena on a date and whoever she says yes to is who she wants to be with. When Jenny sees the texts, she agrees to go on both dates, knowing Serena wouldn't show for either. At Chuck's Saints & Sinners party that night, Juliet and Jenny dress and style themselves exactly like Serena and kiss Dan and Nate, respectively. Later that night, both guys confront the real Serena on playing games with them and each inform her they're done playing her games. After the party, Juliet drugs Serena into an overdose and leaves her alone in a motel room. In Gaslit, Serena is hospitalized for the overdose. When Nate finds out, he assumes Serena did it on purpose for attention and admits to Dan that this is classic Serena attempting to pull everyone back into her games. He vows to not fall for it anymore and gives up on pursuing her.
In the season premiere Yes, Then Zero, Nate and Chuck visit Serena, who is working on a film set in Los Angeles. While there, Nate helps Serena complete a project for her job. Nate later begins working at The New York Spectator, and eventually becomes editor-in-chief (All the Pretty Sources). Serena is also hired to write a blog about herself, titled S by S. In Riding in Town Cars With Boys, Blair and Chuck are badly injured in a car accident and Gossip Girl abandons her site as a result. Soon after, Nate discovers that the car that crashed was ordered for him and he teams up with the replacement Gossip Girl to find what really happened. As a favor, she asks him to delete Serena's blog; which he does. He later tells Serena he did so as a marketing move, and she believes him until she sees the email from Gossip Girl. She then uploads the page behind his back and when Nate finds out, he fires her. Meanwhile, Serena asks Tripp to explain his connection between the car being ordered and a Charlie Rhodes' ex, Max Harding, having an an envelope of cash. Tripp tries to blame the whole ordeal on Maureen, but Nate and his grandfather, William van der Bilt emerge, having been listening to the conversation the whole time. Tripp tells the whole truth and Nate cuts ties with William (Father and the Bride).
When Serena returns to Manhattan from her summer vacation, she brings her new boyfriend, Steven Spence. Meanwhile, Nate has begun dating a journalism student, Sage Spence. While hanging out, Serena and Nate see Steven and Sage together and mistakingly assume they're being cheated on. At Serena's Central Park Conservancy event that night, it's revealed that Sage is Steven's daughter (High Infidelity).
In the series finale New York, I Love You XOXO, Nate is present when Serena marries Dan.
Nate: But you're back now-
Serena: I didn't come back for you! Look, Blair's my best friend and you're her boyfriend and she loves you. That's the way things are supposed to be.
Serena: There's nothing wrong with keeping a secret if the truth is gonna hurt someone!
Nate: That's a hell of a way to look at things.
Serena: Oh, I'm sorry. I didn't realize all of a sudden you're the most honest guy on the planet.
-The Wild Brunch (1x02)
Serena: High school was so much easier.
Nate: In some ways.
Serena: Well, I wasn't attracted to married men.
Nate: Yeah, but I was. Well, not men exactly.
Serena: Lady Catherine. That was my first experience being someone's fake girlfriend. Who knew I'd end up doing it as a profession?
Nate: Two years ago, at the Masquerade Ball, I tried to tell you I loved you. Turns out I told Jenny Humphrey. She was wearing your mask.
Serena: You loved me?
Nate: Of course I did.. Serena, you're the most beautiful, amazing, alive person I've ever known.
-The Last Days of Disco Stick (3x10)
Serena: Nate, I'm really sorry I left the morning after. I never meant to hurt you. I wish that somehow we could relive that night, because this time I'd know that you love me. And you know that I love you.
-The Sixteen Year Old Virgin (3x15)
Serena: Nate, I think I need to be alone for awhile.
Nate: Whoa whoa whoa, wait. I find it in my heart to forgive you for kissing another guy and you're going to break up with me?
Serena: It's not breaking up, it's just taking a break. It's not you-
Nate: Oh, it's not you, it's me? Yes, Serena. It is you. You know, I think it's great that you want to work on yourself. But I'm not going to wait around to see how things go. So if you're out, you're out.
Serena: That's fair. Nate, I love you. I really do. If we're ever gonna have a real chance, this is the only way.
-Last Tango, Then Paris (3x22)
Nate: Serena, you cheated on me with Dan. And then you dumped me and then you disappeared for the whole summer. Then you come back acting as if nothing's changed. But I did. And I guess it took me until now to realize just how mad I am at you.
-The Undergraduates (4x03)
Nate: Dan, I care a lot about Serena, I always will. But whether she realizes it or not, this is how she pulls people back in and I'm not gonna let it happen anymore. Neither should you.