I Am Number Four centers around a boy from an alien planet who is being hunted down by another alien species called the Mogadorians. But he can only be killed once numbers 1,2, and 3 from his world are killed.
Number Four changes his name frequently so he can't be tracked. After learning that Number 3 has finally been killed, he changes his name to John Smith, the name the reader learns to know him by.
John moves to Paradise, Ohio, where he meets his girlfriend, Sarah Hart, and his best friend, Sam Goode. Sam tells John that he has heard of the Mogadorians from a magazine he reads frequently. John's caretaker, Henri, locates the place where the magazine is printed in Athens Ohio.
Henri ventures there first. After sending Henri unanswered texts for two hours, John starts to get worried. Together, Sam and John drive to Athens and rescue Henri from where he is being held prisoner.
Some time later, Henri and Sarah attend a party in which a curtain is lit on fire. Sarah is trapped in the burning house so John has to use his Legacy powers to save her. He reveals who he really is to her and they lie about their escape to the reporters gathered there.
Soon afterwards, John gets the feeling that Sarah is in danger so he races to the school to save her, only to find out that the Mogadorians are already there. Number 6, Henri, and John fight to save her in an epic battle.
In the end, John wins the battle by turning one of the Mogadorians' own beasts against them. The book ends with John leaving Paradise although he promises Sarah he will return for her.