Teenagers Tabitha "Tibby" Tomko-Rollins (AMBER TAMBLYN), Bridget Vreeland (BLAKE LIVELY), Lena Kaligaris (ALEXIS BLEDEL) and Carmen Lowell (AMERICA FERRERA) have all been friends from the day they were born and have never been apart for too long. That's about to change this summer as the very confident and aggressive Bridget heads off to Baja California for soccer camp and sets her sights on soccer coach Eric Richman (MIKE VOGEL). Lena is off to Greece to spend the summer with her grandparents where she ends up being rescued by Kostos (MICHAEL RADY), the grandson of a man with whom Lena's grandfather has feuded for years.
Carmen, who lives with her mom (RACHEL TICOTIN) is off to Charleston to spend time with her father, Al (BRADLEY WHITFORD) who she's barely seen since he left her and her mom years ago. Carmen's hopes of having him all to herself are shattered when she learns that he's about to marry Lydia (NANCY TRAVIS) who has two teenage kids of her own, Krista (EMILY TENNANT) and Paul (KYLE SCHMID). Tibby, meanwhile, is the only one staying home. She works at the local retail giant, Wallman's, to finance her documentary filmmaking and ends up with an unlikely assistant in the form of 12-year-old Bailey Graffman (JENNA BOYD).
The girls' long-distance, connective bond comes in the form of a pair of blue jeans that magically fits all of their different shapes and sizes perfectly. With each keeping the jeans a week before sending them to the next recipient accompanied by a letter detailing the latest in their lives, the girls try to keep in touch and support each other all while dealing with the good and bad events that come their way.