Kuklacı Craig bir gün atölyesinde çalışırken Amerika'nın en ünlü aktörlerinden John Malkovich'in beynine açılan gizli bir yol bulur. Craig bu buluşu iş arkadaşı Maxine'i etkilemek için bir araç olarak kullanmak ister. Bu buluş sayesinde kişi John Malkovich'in beynine gidebiliyor... Fakat zamanla işler karışıyor ve ortaya karışık bir komedi filmi ortaya çıkıyor...

Puppeteer Craig Schwartz and animal lover and pet store clerk Lotte Schwartz are just going through the motions of their marriage. Despite not being able to earn a living solely through puppeteering, Craig loves his profession as it allows him to inhabit the skin of others. He begins to take the ability to inhabit the skin of others to the next level when he is forced to take a job as a file clerk for the off-kilter LesterCorp, located on the five-foot tall 7{u00BD} floor of a Manhattan office building. Behind one of the filing cabinets in his work area, Craig finds a hidden door which he learns is a portal into the mind of John Malkovich, the visit through the portal which lasts fifteen minutes after which the person is spit into a ditch next to the New Jersey Turnpike. Craig is fascinated by the meaning of life associated with this finding. Lotte's trips through the portal make her evaluate her own self...