A brutal storm washes over a small town in Maine. The day after the storm struck, a mystifying and unexplained fog hovers over the town. Soon, some residents begin to realize that there are some monstrous and deadly animals creeping around in the fog waiting to destroy everything and anyone in their path. A portion of the town's citizens become trapped in the local grocery store. The small group of townspeople break into two factions. David Drayton, an artist, leads one group of people. The other group is led by Brent Norton who is a neighbor of Drayton's and does not always get along with him. Drayton believes that there are monsters in the mist and Norton feels that there are not. Eventually, the group led by Norton leaves the grocery store and disappears into the dense fog. At this point in the movie, it is unclear if any of them make it to safety.
The small group that chooses to stay inside the safety of the store also splinters into two groups. Another group forms and is led by a bible holding religious fantastic named Mrs. Carmody who believes that the town is in the midst of a biblical apocalypse. Mrs. Carmody convinces more and more of the people in the store to her side. Mrs. Carmody begins to sway the people in her group to believe a human sacrifice is the only way out. Eventually, the two remaining groups decide to put their differences aside to fight the monstrous creatures. However, the truce is temporary and another battle occurs when David and his group decide it is better to go outside and face whatever is in the mist.
After a violent confrontation, David and a few others leave the store in hopes of finding a way out but quickly find that the town and its people are all nearly destroyed. David and the others sense death is inevitable and make a horrifying decision that brings the film to a traumatic climax and a surprisingly traumatic ending.