Earthquakes begin occurring in New Orleans as the result of a fracking operation. Bus driver Charlie is called in replacement for another driver who is out sick, and has to drive a group of cheerleaders. In the meantime, his wife Katelynn, and children Justin, and Annabel go on a bus tour around the city. On the bus, they meet the driver Paul, whose family, consisting of sister Petra, and father Roy, run a boating tour business in the swamps. Among the other guests are couple Ernie, and Tina, and an old man whom Paul nicknames "Gramps". The group has an encounter with several giant albino spiders, and stop at a drug store to grab bug spray. However, more spiders invade the store, killing Gramps, and a clerk, and the group is eventually forced back to the bus. They drive to the marina where Roy, and Petra work, the both of whom are already aware of the situation. After Ernie is abducted by a spider, the survivors flee on Roy's boat, and soon run aground in a nearby forest. Tina is thrown from the boat during the crash, and is dragged away by another spider while the others flee into the woods. Meanwhile, Charlie's bus is attacked by the spiders, and he crashes it into a tree. He, and the cheerleaders manage to stay safe inside as the spiders encase the bus in webbing, although a group of soldiers arrive, and kill the spiders before rescuing the passengers.Paul's group meets up with locals Jean Jacques, Roux, and Guillaume, and they take the group to a warehouse they work at. There, Katelynn, a biologist, suggests they trap a spider so she can examine it. They do so, and Katelynn discovers that the spiders are prehistoric, and were released from the earthquakes. She also explains they are a hive mind, and, if they can find, and kill the queen, they will all die. The warehouse soon comes under attack from the spiders, and the survivors run into the woods; in the ensuing chaos, Roux, Guillaume, and Roy are killed, and Katelynn, and Petra are abducted while Justin, and Jean are evacuated on a helicopter. Paul, and Annabel venture into a nearby cave to find a nest, with Katelynn, and Petra both trapped by webbing. They free them, although the queen spider soon attacks the group; they manage to reach the boat, and launch it back into the water. Meanwhile, Justin, and Jean are taken to a rooftop where Charlie is, and he reunites with his son.On the boat, Katelynn falls unconscious due to an asthma attack, and Paul resolves to kill the queen himself. He gears up in a diving suit, and heads into the city where the queen is on a rampage as Annabel, and Petra find an ambulance to get Katelynn to the hospital. Annabel reunites with Charlie, and Justin on the rooftop as Jean enters the city streets to help Paul. The two are abducted by the queen as she creates a giant web between two buildings. Jean is soon killed, and Paul is swallowed whole by the spider, although he sticks a piece of dynamite inside its body, and attaches a rope to it before falling out the spinneret. Paul uses an explosive to ignite the rope, the spark eventually reaching the dynamite, causing the queen to blow up from the inside out, killing it. Paul is rescued by military forces, and reunites with Petra as all of the remaining spiders soon die.