Set in the fictional small town of Tree Hill, North Carolina, this teen-driven drama tells the story of two half brothers, who share a last name and nothing else. Brooding, blue-collar Lucas is a talented street-side basketball player, but his skills are appreciated only by his friends at the river court. Popular, affluent Nathan basks in the hero-worship of the town, as the star of his high school team. And both boys are the son of former college ball player, Dan Scott, whose long ago choice to abandon Lucas and his mother Karen, will haunt him long into his life with wife Deb, and their son Nathan.
As Brooke and Julian begin to adjust to life with their new children, Haley and Nathan find themselves dealing with similar issues. Although they don't know it yet, faces from the past threaten to interrupt plans for all their futures. Meanwhile, a mysterious problem arises for Clay and Quinn.
Brooke and her father discuss a new business venture; Julian worries about his investment; Quinn talks Clay into getting help; Millie tries to be honest with Mouth; Alex receives a tempting offer.
Dan helps a struggling Haley at Karen’s Café. Meanwhile, Quinn discovers that Clay is hiding something from her, and Chase tries to mend a broken heart. Brooke is let down by her lunch plans with her dad, and Julian makes a life-changing mistake.
As Julian deals with his guilt, Brooke helps Haley confront a new rival cafe, and its difficult owner. Meanwhile, Chase's new girl has a complicated secret, and Quinn takes extreme measures that help Clay realize he's worse off than he thought.
As Quinn distracts Jamie, Haley searches for Nathan. Clay finally gets answers about his condition. Meanwhile, Julian attempts to get back to a normal life, while Brooke tries to give Tara a chance.
Dan enlists Julian to help in his search for Nathan. Mouth fills Clay in about Nathan, as Haley explains Nathan’s disappearance to Jamie. Brooke gets an idea of how to bring patrons to an empty Karen’s Café, and Chris Keller confronts Chase about Tara.
Haley seeks help from Lucas as Nathan (James Lafferty) makes an escape attempt. Brooke comes face-to-face with Xavier. Juliain uncovers evidence that assists Dan in his search for Nathan. Clay makes a connection with another patient.
Haley receives news of a possible tragedy. Dan’s search for Nathan leads him back to his dark past. Clay has a breakthrough in his treatment. Brooke and Julian deal with Xavier. Chase’s concern for Chuck pushes him to his limits.
Brooke and Julian take new measures to protect their family. Skills helps Mouth get to a turning point, and Chase faces consequences for defending Chuck. Clay reaches a new understanding with Logan.
Dan, Julian and Chris Keller attempt to rescue Nathan. Brooke’s conflict with Xavier escalates. Quinn and Clay revisit the past.
The search for Nathan becomes increasingly dangerous, and Dan’s life hangs in the balance. Brooke is surprised when her father returns. And Clay and Quinn reconnect with Logan.
As Haley prepares to emcee the annual Tree Hill Burning Boat Festival, Brooke uses the opportunity to process her father’s betrayal, while Julian tries to breathe new life into a past idea. Mouth and Millie make a change to their morning show, and Clay and Quinn get ready for Logan’s first night at the beach house.
In the final chapter of One Tree Hill, the tenth anniversary of Tric brings old faces and new possibilities for the Tree Hill family.