Larry Daley is a divorced father who can't seem to keep a job for more than a week. As a last resort, Larry applies for a job as a night shift security guard at the American Museum of Natural History. However, a seemingly easy job turns out to be an adventure when he finds that an ancient curse causes the "inhabitants" of the museum to come to life at night.

Get ready for the wildest and most adventure-filled night as Larry spans the globe, uniting favorite and new characters while embarking on an epic quest to save the magic before it is gone forever.