Hazel Grace Lancaster is an intelligent and sarcastic Indianapolis teenager coping with terminal thyroid cancer that has metastasized to her lungs. Believing her to be depressed, Hazel's mother urges her to attend a cancer patients' support group at a local church to make friends. During a support meeting, Hazel meets Augustus Waters, a teen who had suffered from osteosarcoma that caused him to lose his leg. After the meeting Augustus invites Hazel to his house, where they bond over their similar interests and views on cancer. Before she leaves, they agree to read each other's favorite novels. Hazel recommends to Augustus An Imperial Affliction, a novel about a cancer-stricken girl named Anna that parallels Hazel's own experience. After Augustus finishes reading her book, he is frustrated upon learning that the novel ends abruptly without a conclusion. Hazel explains that the novel's mysterious author, Peter van Houten, had retreated to Amsterdam following the novel's publication and has not been heard from since.

Weeks later, Augustus reveals to Hazel that he has tracked down Van Houten's assistant, Lidewij, and, through her, has managed to start e-mail correspondence with Van Houten. Hazel writes to van Houten with questions regarding the novel's ambiguous ending, to which van Houten replies explaining that he can only answer Hazel in person. Hazel proposes the trip to her mother, but is rejected because of financial and medical constraints. Later, Augustus surprises Hazel with tickets to Amsterdam, attained through a charitable foundation similar to the Make-A-Wish Foundation, namely The Genie Foundation.

Days before the trip, Hazel suffers an episode of pleural effusion and is sent to the ICU, prompting her doctors to question the safety of overseas travel. The medical team argues against the trip but eventually complies with Hazel's parents to accommodate her travel. When Hazel and Augustus first arrive in Amsterdam, they go to a restaurant and find out that Van Houten paid for a meal and champagne on their behalf. Augustus then confesses his love for Hazel that night. Hazel and Augustus finally meet van Houten, but are shocked to find that, instead of a prolific genius, he is a mean-spirited drunk. Lidewij confesses to having arranged the meeting on his behalf, angering van Houten, who proceeds to insult Hazel's cancer and refuses to answer any of her questions. The two leave the author in anger and disappointment.

Accompanied by Lidewij, Hazel and Augustus visit the Anne Frank House. Hazel struggles to climb the many stairs and ladders leading up to the attic but by the end of the tour, Augustus and Hazel share a romantic kiss, followed by applause from the other tourists in the attic. They return to the hotel and have sex for the first time. The next day, Augustus confesses that a recent PET scan revealed his cancer to have relapsed. Resolute, the two affirm their love and support for each other. Upon their return to Indianapolis, Augustus' health significantly worsens. He ends up in the ICU for a few days and realizes that he is really down to his final days. Augustus invites Isaac, his blind best friend, and Hazel to his pre-funeral, where they speak his eulogies. Hazel quotes van Houten about "larger and smaller infinities" and confides that she would not trade their short time together for anything in the world. Augustus dies eight days later.

At the funeral, Hazel is astonished to find van Houten in attendance. He explains that he and Augustus maintained correspondence after Amsterdam and that Augustus had demanded he make up for ruining their trip by attending his funeral. He confides in Hazel that his novel is based on his own daughter, Anna, who died from cancer at a young age. In an attempt for forgiveness, van Houten tries to reveal the fate of Anna's mother and gives Hazel a piece of paper. Hazel, still upset with his behavior, crumples up the paper and asks him to leave. Later, while talking with Isaac, Hazel learns that Augustus had asked van Houten for assistance in writing his eulogy. Realizing what van Houten had given her, she retrieves the crumpled paper and reads Augustus' words, which state his acceptance of death and his love for Hazel, a sentiment she returns. The film ends with Hazel lying on her back on her lawn looking up at the stars; she smiles as she remembers Augustus.