In New York, the unemployed divorced Larry Daley is a complete loser. His son Nick is very disappointed with his father that is gong to be evicted, and Larry accepts the job of night watchman in the Museum of Natural History as the substituted for three old security guards that have just retired to raise some money and pay his bills. In his first nightshift, Larry realizes that everything at the museum comes to life at night. The Museum transforms in a complete chaos with the inexperienced Larry, and he learns that since an old Egyptian stone came to the Museum in 1950, the was statues comes to life until dawn. When Larry brings his son to spend a night with him, the three old guards break in the Museum to stole the magic stone. Larry organizes the historic characters to help him to arrest the criminals and save the museum.