In 2003, John Tyree (Channing Tatum), a Staff Sergeant in the United States Army Special Forces is lying on the ground in combat gear with multiple gunshot wounds to his body. Coins begin to fall over him as, in a voiceover; he recalls a childhood trip to the U.S. Mint. He compares himself to a coin in the United States Military, and states that the last thing he thought about before he blacked out was "you".
In 2001, in Charleston, South Carolina, John is on vacation. He meets Savannah (Amanda Seyfried), a college student on spring break, when he rescues her purse from the water. Over the course of two weeks, Savannah and John fall in love. John meets Savannah's family, her neighbor, Tim Wheddon (Henry Thomas), and Tim's son, Alan (Luke Benward) who has autism.
Savannah meets John's father (Richard Jenkins), a reclusive man who seems to be obsessed with his coin collection (specifically mules), but his genuine interest draws her, to John's surprise. Savannah mentions to John that his father, like Alan, may have high-functioning autism. This upsets John, who storms off, and then gets into a fight with Savannah's friend Randy (Scott Porter) and, in the process, accidentally punches Tim. John apologizes to Tim, leaves Savannah a note, and then they spend one last day together, parting with, "I'll see you soon then" rather than goodbye.
John and Savannah continue their relationship through letters, expecting to build a life together when he leaves the army. But the recent September 11 attacks make him reconsider the army, and he ultimately chooses to re-enlist. Over the next two years, the romance goes on, through their letters. After a time, John finds himself anxiously awaiting the next letter, but when it arrives it is a Dear John letter, informing him that she has become engaged to someone else, John burns all of Savannah's letters.
Despite being wounded and encouraged to return home, John re-enlists. After four more years and many missions, while waiting to receive orders on his unit's next deployment, John is informed that his father had a stroke. When John arrives at the hospital he learns that his father is still alive but in grave condition. John writes a letter to his father, which he reads to him at the hospital; John's voiceover at the beginning of the film was from this letter, in which he told his father that the first thing to cross his mind after he was shot was coins, and the last thing to cross his mind before he lost consciousness was his dad, ultimately the most precious person in his life. Soon afterwards, his father sadly dies.
John goes to visit Savannah and is shocked to find that she has married Tim and is living with him. He learns that she had to abandon her dream of a riding camp for kids with autism because of Tim's fight against lymphoma, and John goes with her to visit him in the hospital. Tim tells John that Savannah still loves him and she has never forgotten him. That night, Savannah asks John to stay for dinner. At the table, John asks Savannah why she did not even call him and she says it was because just hearing his voice would make her change her mind. As John goes towards the door, Savannah says "I'll see you soon then". She asks him to reply the same (like they always do) but there is silence. John could not say it back because it wouldn't have the same meaning as before. John stands at the door struggling inside to decide. Savannah asks for him to say it back once again. He replies "Goodbye, Savannah" and leaves, which leaves Savannah crushed and heartbroken. John drives away knowing the decision to let her go had killed him inside. John makes a decision to sell all of his father's coin collection except the mule that John found, to raise money which could help Tim in his treatment. Back in the army, it shows John using the mule as a charm. It then shows John receiving a letter from Savannah telling him that Tim died after two months and ending with "I'll see you soon, then." The film then skips forward to show John as a civilian, having left the army, carrying his bike. He sees Savannah in a coffee shop, and they make eye-contact. The last scene ends with both of them warmly hugging one another outside the coffee shop.