The Curious Case of Benjamin Button is based upon a 1922 story by the same name written by F. Scott Fitzgerald. The film revolves around a character, Benjamin Button who ages in reverse due to a genetic defect. The storyline tries to capture the dynamics of his relationships with several people throughout his life and how his condition affects those relationships. Whether it's his 'mother', his early friends, his real father, or, his love-interest, his reverse aging creates complexities that he fails to comprehend throughout his life.

As a prelude, the films starts with a mention of a clockmaker named Gateau who is commissioned to make a clock at New Orleans train station after the WW1 has ended. He intentionally makes a clock that runs backward, hoping to go back in time and bring all those back who have died in the war including his only son. This small story has a profound symbolic effect on the main plot of the story. The film depicts what will actually happen if the clock were to actually run backwards in time.

The story is narrated by a 81-year old woman, named Daisy (Cate Blanchett) on her death bed. She narrates the story to her daughter Caroline, while the hurricane Katrina lurks in the air and can hit the hospital anytime. The hurricane also has a symbolic meaning; Daisy's story has a secret that will bring a storm in the life of Caroline.

Brad Pitt as Benjamin Button is tremendous. Starting out as an old man with feeble body but young mind, he portrays the emotion of a child trapped in an old body fantastically. The main plot revolves around Benjamin and Daisy's love story and how due to Benjamin's condition they could never live a life together. Most tragic part of the story is how Benjamin grows younger while Daisy gets older until one day when Benjamin dies as an infant in the arms of her lifelong sweetheart Daisy.