Joel Barish (Jim Carrey) is an emotionally withdrawn man and Clementine Kruczynski (Kate Winslet) is his girlfriend who is a dysfunctional free spirit. They are inexplicably attracted to each other despite their different personalities.

They do not realize it at the time, but they are former lovers now separated after two years together. After a nasty fight, Clementine has had her memories of their relationship erased from her mind. Upon learning this, Joel is devastated and goes to the doctor to have the same procedure done. However, while unconscious, Joel has second thoughts and decides he wants to keep his memories of Clementine.

Much of the film takes place in Joel's brain as he tries to find a way to preserve his memories of Clementine, and two Lacuna techies Patrick (Elijah Wood) and Stan (Mark Ruffalo) try to erase the memories. We watch their love and courtship go in reverse: The memories are slowly erased while Joel tries his best to resist the procedure and hide inside his mind.

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