The book starts off at the end of a big storm in Bridgton, Maine. As the residents are cleaning up from the storm, they notice a thick mist coming from off the nearby lake, coming from an area used by “Project Arrowhead”, which is a mysterious military installation. The main character, David Drayton, takes his son and neighbor to go to the town supermarket, leaving his wife behind. At the supermarket, the mist rolls through the rest of town and envelops the supermarket. A man runs into the market, bloodied and screaming about something hidden in the mist. He runs back outside and isn’t seen again.
After some time, when nothing seems to happen, David’s neighbor organizes a group of people to leave the store, saying nothing is going to happen. David, who is skeptical, persuades his neighbor to tie a rope around his waist, so that the supermarket survivors will know that he made it at least as far as the rope goes. The group ventures out and, needless to say, they do not make it as far as the rope’s length. This event, combined with the discovery of a twin suicide of Project Arrowhead soldiers in the store, lead many to believe that whatever is hiding in the Mist is the end of the world. This leads to a dangerous situation, when an older survivor, Ms. Carmody, begins talking about the biblical implications and starts talking about a human sacrifice, eyeing David’s son and Amanda Dumfries, a fellow survivor whom David eventually makes love to, both of them theorizing that their significant others have likely fallen victim to the mist and both of them needing human contact to survive the terrible ordeal. During this time, the supermarket becomes under attack from creatures in the mist. At the front of the store, giant mosquito-like bugs attach themselves to the front windows and one crashes into the store and has to be burned alive. At the back of the store, after seeing strange movements and hearing strange sounds at the delivery door, the group tries to open it slightly. A tentacle shoots under the door and grabs one of the survivors, pulling them violently out into the mist.
Sometime during these attacks, David begins to theorize that the creatures can only hunt by smell, and decides to try to make an escape to a car with a few other survivors. This comes at the moment when Ms. Carmody’s group decides to come for David’s son and Amanda. The tensions climax when the store owner, Ollie Weeks, shoots and mortally wounds Carmody.
David and company run out into the Mist where they finally get their first glimpse at some of the creatures, like a giant spider that shoots acidic webbing, giant squid, and giant lobster-like creatures. Although about half the group falls prey to the creatures, once David and the rest get into the car and shut the door, his theory is proved correct, as the creatures retreat. David attempts to go back to find his wife, but as he begins to approach his street, he can hear several creatures in the woods, and knows that his wife did not make it. Instead, he turns around and makes a break for another state, hoping the Mist has not spread everywhere. On their way out of Maine, they drive under a creature much larger than any of the ones seen outside the store, this one being the size of a building and having several of the mosquito like bugs clinging to its underbelly. The story ends with David and his son continuing to drive, hoping that they will find a place where the Mist has not reached, but uncertain of what will happen when the car runs out of gas.