Adaline Bowman (Blake Lively) is seen purchasing fake IDs at an apartment in San Francisco. She goes home to her apartment where her dog greets her. During her 107 years of being alive, she has raised the same kind of dog over and over again. She notes that she is late for work at the downtown library’s office of archives.
While working, she opens a film reel and her life is explained. She was born on New Year's Day in 1908, got married, had a child, and became a widow. One night, an unexplainable snow began to fall as she was driving to her parents' house. She suffers a car accident during a rare snowfall in Sonoma County, she dies in frigid waters and brought back to life by a lightning strike, the combination that causes her to remain 29 years old forever. As her daughter Flemming (Ellen Burstyn) grows older, it becomes apparent that Adaline is not aging. One day she is pulled over by a cop, who takes away her ID as it says she is in her late 40s.
One night, she is walking home when two FBI agents put her in a car and try to take her on an airplane. She escapes and decides she will spend her life running. She explains this to Flemming, and they have a heartfelt goodbye. At present day, she adds a cosigner - her next identity, to her bank account and has a flashback when she opened the account triggered by the picture of her bank manager from years ago, which is on the wall. She had invested in Xerox, and it has paid off well. She is planning to leave soon to live in Oregon, a remote location to avoid questioning and possible suspicion.
On New Year's Eve, she attends a party where she meets Ellis Jones (Michiel Huisman). Who, after flirting with each other in an elevator, mentions that he wishes to bring her flowers but cannot, as he doesn't have her address. The next day at work, her coworkers mention that a generous benefactor is coming to donate some books. Ellis brings her books that have flowers in the name, but Adaline refuses to go out with him. He then says he’ll withdraw his donation if she declines the date. For their date, they visit the tunnels containing an old boat under San Francisco. Adaline later agrees to a second date with Ellis. She goes to Ellis’ apartment for the next date, and they spend the night together.
In a flashback, Adaline is shown pulling up in a cab to a man on a park bench, fiddling with an engagement ring. Adaline, looking scared, asks the cab to keep driving. Present day, she ignores Ellis’ calls. He shows up at her apartment, and Adaline pushes him away. While looking through old photographs, she has a change of heart. She goes back to Ellis’ workplace to apologize. They go on a date to an old covered drive-in movie theater. He asks her to attend his parents’ 40-year anniversary party, and she says yes. They enter his home, and she is greeted by William Jones (Harrison Ford), who calls her Adaline. She says that was her mother. He’s shaken and says they were “very close.”
A flashback explains how they met. Adaline was having car trouble in England, and he was a soldier studying medicine overseas. They returned to the United States together. She pushed William to follow his dream of astronomy instead of medicine. He was the one with the engagement ring. That night, they play trivia. Adaline pretends to not know an answer but after a diss by Ellis, she goes balls to the walls and wins. The family jokes that they didn’t know what would happen first: William’s loss in trivia or the arrival of Della – a meteor he predicted would come that was Adaline’s nickname.
The day of the party, Adaline talks to William and he notices a scar on her left hand from stitches he made while they were hiking decades ago. He realizes it is Adaline that left him on the park bench years ago because she does not age. He begs her not to run, for Ellis's sake, but she says she doesn't know how. She writes a note to Ellis, packs, and leaves.
Adaline is driving in the woods when she stops and calls Flemming to tell her she will stop running. As she turns the car around, a tow truck plows into her, a hit and run, leaving her to die. A meteor hits the moon in 1178, setting off a chain of events that now creates snow falling in Sonoma County for the first time in 78 years. While freezing and helpless she dies again. An ambulance arrives and she is revived by an EMT's defibrillator (similarity to her first death being revived by lightning strike). In the hospital she wakes up to Ellis. When her daughter arrives, Adaline lets her know she has told Ellis the truth.
Some time later, Ellis and Adaline, are going to a New Year's Eve party. As she is leaving, Adaline sees something strange in the hallway mirror. She finds and plucks to hold up in the light, her first gray hair. Apparently, a combination of the defibrillator and hypothermia from the car accident have resumed her normal aging process.
The last scene shows the meteor Della flying by earth 50 years later than Williams prediction (about the same amount of time between William seeing Adaline again).