In the sixth season premiere, the residents of Tree Hill are each faced with choices that will change their lives forever. As Lucas goes after the woman he wants to spend his life with, Brooke must deal with her mother being back in her life. Meanwhile, Mouth and Millicent make a large step in their relationship; Dan has an encounter with a person from his past; and Peyton finally gets to live out her dream.

As Tree Hill residents learn of a surprise marriage, Brooke must deal with life after the Clothes over Bros robbery. Meanwhile, Nathan and Haley cope with their own devastating news, as well as the fact that Carrie has re-entered their lives; while Dan finds himself stuck under Carrie's grips.

Lucas returns to coaching the Tree Hill Ravens after his time in Las Vegas and must help the team through a tragedy. Meanwhile, Nathan and Haley must find a way to explain the death of someone close to them to Jamie.

Lucas struggles to find a way to inspire his team as Haley begins to look into Dan's disappearance. Meanwhile, Brooke confronts a demon from her past; Nathan begins to deal with Deb's relationship with Skills; and Peyton is shocked when a famous musician visits her at the studio.

As Lucas and Lindsey reunite for a business meeting, Nathan receives the offer he has been waiting for since he was little. Meanwhile, Haley unknowingly puts Jamie's life on the line; Brooke struggles with her decision concerning Clothes over Bros; Peyton uncovers a secret regarding her new artist; and Haley ends the feud with Carrie once and for all.

As Lucas sets out on his book tour, he runs into a person from his past. Nathan finally gets a chance to prove himself on the court, but begins to question his health as he does so. Meanwhile, Haley reaches out to a student; Brooke debates a life-changing decision; and Peyton confronts Mick over his true identity.

Nathan and Haley must team up to help Jamie deal with a school bully. Meanwhile, Lucas and Peyton continue to adjust to life as a live-in couple. Elsewhere, Mouth tries to get his old job back.

Lucas’ novel receives interest from a suprising person, as does Mouth as he meets his new intern. Jamie begins to develop a crush on Sam and her rebellious ways, while someone becomes enamored with Brooke. Meanwhile, Haley and Nathan discuss his return to baskeball as his comeback begins to look more like a reality.

The past comes back to haunt the residents of Tree Hill, as deception and relationship problems take center stage. Nathan must go head-to-head with an old rival as Brooke must face someone who hurt her in the past. Meanwhile, Lucas' novel takes him into a threatening situation.

Tension arises backstage at Peyton's USO show as Lucas deals with Peyton and Julian's past. While Haley tries to find a way to ease her stage fright, Nathan grapples with a decision that could forever change his career. Meanwhile, Brooke receives a call that could end her relationship with Sam and Millicent confronts Mouth over Gigi.

In an episode written by series star Chad Michael Murray, classic films are given a nod when Karen’s Cafe is transformed into a nightclub with Lucas as its proprietor.

Lucas heads to Hollywood to meet the director of the film while Nathan lands a try-out with a pro basketball team. Meanwhile, Peyton works to get Mia to focus on her follow-up album; Millicent confronts Mouth about Gigi; Julian asks Brooke to design clothes for his film; and Haley takes Jamie to his school talent show.

Peyton shares shocking news with Lucas who is still in Los Angeles with Dixon and Julian. Nathan struggles to adjust to his new career and Brooke desperately searches for Sam.

In the fourteenth episode (s6e14) news of Peyton’s condition spreads to the rest of the friends soon although Peyton hesitates to share it with Brooke. However Brooke is preoccupied with figuring out Julian’s intentions. On the other hand Lucas and Peyton keep an eye on Jamie as Nathan and Haley go out on a date. Millicent makes an unsuccessful attempt to patch up with Mouth.

Lucas and Julian work to find the perfect director for their movie while Peyton is unsure what to think about a gift from Lucas. Meanwhile, Brooke deals with her relationship issues.

In the sixteenth episode (s6e16) Lucas is preoccupied with casting for his movie and it is left to Peyton to make all the wedding arrangements on her own. Brooke meets the actress who will play her role in the movie. Nathan gets lovely news and Haley has a difficult choice to make at work. Granddad Dan helps Jamie to deal with his infatuation.

Peyton and Lucas deal with shocking news about Peyton's pregnancy as Brooke and Julian face a crossroads in their relationship. Meanwhile, Nathan and Haley celebrate their anniversary, with Dan and Deb babysitting Jamie; and Mouth and Millie work to redefine their relationship.

As Lucas and Julian face a setback in their film production, Peyton and Haley team up to help Mia with her new single. Meanwhile, Brooke faces a crisis when Sam is arrested; and Jamie learns the truth about Dan and Keith.

While Julian makes Brooke a surprising offer, Lucas takes Nathan and Jamie to an important place from his past. Meanwhile, Peyton prepares for the future; Sam and Jack go up against the principal who fired Haley; and Skills and Mouth go on a road trip to help Mouth forget Millie.

When Peyton's pregnancy is threatened, Lucas has a hard time dealing with the aftermath. Victoria returns to Tree Hill to try to convince Brooke to come back to Clothes Over Bro's. Meanwhile, Haley and Nathan debate pulling Jamie from his school as Mouth and Millicent try to put their relationship back together.

As Brooke uncovers something that could change Sam's life, Nathan begins to question his dream to play in the NBA when Haley receives an unexpected offer from Nick Lachey. Meanwhile, Jamie and Skills go to Jamie's first school dance; and Lucas and Peyton take a road trip.

The families of Tree Hill draw closer as Lucas bonds with Jamie while working on Peyton's car, Sam develops a connection with Victoria, and Brooke and Haley throw Peyton a baby shower. Meanwhile, Nathan's ambitions seem closer than ever when he learns that an NBA scout will be watching his next game...

Peyton and Lucas' wedding day arrives, and it's full of surprise guests. Haley winds up playing an unexpected role in the ceremony as Nathan waits for his call from the NBA. Meanwhile, after losing him at Lucas' first wedding, Skills keeps a close eye on Jamie the second time around.

Nathan is released from the Chiefs, and struggles with a way to break the news to Haley and Jamie. As Peyton's delivery day approaches, Lucas and Peyton receive a surprise visit from Karen. Meanwhile, Dan finds himself on death's door, still waiting for a transplant; and Brooke and Victoria work to re-launch Clothes Over Bro's.