Carmen buys a pair of jeans at a thrift shop. Magically, the pants fit Carmen and her three best friends, Lena, Tibby, and Bridget, equally, even though the girls have very different bodies. The girls, who “met” before birth when their mothers were in a prenatal aerobics class together, are spending this summer apart—their first significant separation. Carmen will go to South Carolina to spend the summer with her father. Lena will go to Greece with her sister, Effie, to spend the summer with their grandparents. Bridget will spend the summer at soccer camp in Baja California, Mexico. Only Tibby will stay home in Bethesda, Maryland, to work at Wallman’s, a superstore. Before each girl sets off to her summer destination, they have a friendship ceremony at Gilda’s gym, where their mothers met so many years ago. To stay close while they’re apart, they vow to send the pants—which they call the Traveling Pants—to one another throughout the summer.
Tibby immediately hates Wallman’s and decides to make a “suckumentary” about her summer, since she knows she’ll continue to hate everything and everyone. Meanwhile, Carmen is devastated in South Carolina when her father surprises her with big news: he’s engaged, and his fiancée, Lydia, has two teenage stepchildren, Paul and Krista. Carmen, who is half Puerto Rican, feels out of place in this new family. In Greece, Lena’s grandmother tries to set her up with a Greek boy named Kostos, but Lena wants nothing to do with him. She doesn’t trust any boys and assumes that if Kostos likes her, it’ll be only because she’s beautiful. Bridget develops a crush on Eric, a coach at soccer camp.
One day at work, Tibby sees a young girl collapses in the store and rides with her in the ambulance. In the days that follow, she meets the girl, whose name is Bailey, a few more times. Bailey is twelve and has leukemia. She’s fascinated with Tibby’s film, and Tibby reluctantly lets her start helping. In South Carolina, Carmen does not settle in well. She hates the new family, and she’s rude to everyone, even when she finds out that Lydia’s ex-husband was an alcoholic. She’s sick of hearing everyone talk about her father’s upcoming wedding. Meanwhile, Bridget starts flirting relentlessly with Eric, trying to get him to notice her even though he’s older than she is and a coach. She convinces a few of her new friends to sneak to a nearby bar with her one night, where she dances with Eric. When she plays soccer, she plays too aggressively, angering her coach.
In Greece, Lena spends her days painting, walking, and trying to get closer to her grandparents. One day, she goes skinny-dipping in a beautiful, isolated pond—and Kostos sees her. She assumes he was spying on her and storms home angrily, her clothes askew. She doesn’t correct her grandparents when they assume that Kostos attacked her, and her grandfather punches Kostos’s grandfather. Still, Lena can’t bring herself to tell the truth about what happened. She’s surprised to find that she’s upset when Kostos starts ignoring her.
Tibby and Bailey interview a video game player named Brian McBrian, and Tibby finds him more interesting than she expected to. Next, they interview Margaret, a woman who has worked for years at the movie theater. Expecting to mock her, Tibby instead feels bad for Margaret, since she’s obviously very lonely. Her documentary is turning out to be different than she expected.
Carmen goes with Lydia and Krista to try on a bridesmaid’s dress, which doesn’t fit her at all. She storms out of the shop, insulting Lydia on her way out. Later, her father and everyone else act like nothing happened, and Carmen runs out of the house. She expects her father to follow her or come out looking for her, but he doesn’t. Eventually, Carmen goes home and sees her father and his new family calmly eating dinner around the table. Enraged and jealous, Carmen throws a rock through the window, breaking it, and she then flees. She takes a bus back to Bethesda.
Bridget sneaks to Eric’s cabin and wakes him up. He doesn’t immediately pull away from Bridget when she touches his head and chest, but eventually he tells her to leave. Bridget takes his words as encouragement. Bridget is determined to make something happen, so she visits him again at his cabin a few nights later. This time, he gives in to her, and they have an intimate encounter. Later, Bridget is very upset, and she can’t get out of bed. She’s listless for many days. On the day of the big soccer match, Bridget explodes at the coach and leaves in the middle of the game. Eric tries to comfort her about what happened between them, but Bridget is too upset.
Carmen feels immensely guilty about what she did, but she doesn’t know how to make it right. She sends her father an envelope full of money to help fix the broken window. When she finally gathers the courage to call her father, she lets her anger come through. She tells him how hurt she is that he left her and her mother and has a new family. She decides to surprise her father, so she flies to South Carolina and goes to the church on the day of his wedding. They promise to be more honest with each other from now on.
Lena is distracted and unable to paint, and she’s upset because Kostos has been ignoring her. She walks back to the pond, and this time she sees Kostos swimming naked. She realizes he hadn’t been spying on her that day, and that this is his secret place to swim. At home, she paints a picture of Kostos. Her grandmother tells her that, years ago, Kostos’s parents and brother were killed in a car accident.
One day, Bailey doesn’t show up at Wallman’s to meet Tibby after her shift, which she’s done reliably all summer. Tibby is alarmed and finds out Bailey is in the hospital. When she gets there, Bailey’s mother tells Tibby that Bailey has gotten an infection and may not recover. Mimi, Tibby’s guinea pig, dies. Tibby can’t face the truth and puts Mimi’s dead body in the freezer. She begins ignoring phone calls from Bailey and Bailey’s mother. Carmen hears one of these calls and convinces Tibby to visit the hospital. Tibby finally does and sees that Bailey is not doing well. A few days later, Bailey dies. The night after the funeral, Tibby buries Mimi near Bailey’s grave.
Effie sees Lena’s picture of Kostos and realizes that Lena is in love with him. She convinces Lena to tell Kostos how she feels, since their time in Greece is almost over. When Lena finds Kostos, she gives him a painting she did of the olive grove near the pond, and she tells him how she feels. They kiss. The next day, on the plane home from Greece, Lena decides to go to Mexico and help Bridget, who she knows can have a hard time recovering from her sadness. She gets to Mexico in time to help Bridget get home.
When all the girls are back in Bethesda, they gather for a birthday celebration at Gilda’s. They write down their experiences on the Pants and begin reacquainting themselves with one another.