Ko Susan Murphy na njen poročni dan zadane meteor in jo spremeni v velikanko, jo nemudoma odpelje oddelek za pošasti. Tam spozna skupino drugih pošasti, ki jo sestavljajo nori znanstvenik v telesu žuželke, mešanec med ribo in sesalcem, želatinasta stvor brez možganov in ogromna žuželka. Ko Zemljo nekega dne napadejo nezemljani, so Susan in njeni novi prijatelji edini, ki lahko rešijo svet pred grozečim uničenjem.
When a meteorite from outer space hits a young California woman named Susan Murphy and turns her into a giant monster, she is taken to a secret government compound where she meets a ragtag group of monsters also rounded up over the years. As a last resort, under the guidance of General W.R. Monger, on a desperate order from The President, the motley crew of Monsters is called into action to combat the aliens and save the world from imminent destruction!