After the Graboid incursion in 1989, Graboids weren't seen again in the small town of Perfection, Nevada and were believed to be extinct there. Despite this, Jack Sawyer capitalized on the original event to run fake Graboid tours while paranoid survivalist Burt Gummer set up monitoring equipment to keep an eye out for more Graboids, not believing them to be truly gone. Despite giving the equipment to the other residents of Perfection as well, they failed to maintain it in the 11 years that followed, believing the threat to be gone.
In 2001, shortly after the Graboid incursion in Argentina, three more Graboid eggs hatched in the valley and the Graboids were once more active in Perfection. Only Burt had maintained his equipment and knew of the threat and quickly alerted the town. However, during Jack Sawyer's Graboid tour, an actual Graboid showed up and ate Jack's partner Buford. With the help of Mindy Sterngood, a young survivor of the original incursion, the rest of the tourists and Jack got away. Following the revelation of the Graboids return, Burt gathered the town and informed them that there were only three Graboids this time and to prepare to hunt them. Nancy Sterngood objected as this time they weren't completely cut-off and could call the government for help, but Burt was adamant that they needed to deal with the threat themselves as they didn't know how long the Graboids had been active and thus how long it was until they became Shriekers. The next morning, armed with Burt's homemade explosives and RC cars, Burt, Jack and Miguel Sanchez prepared to go hunt the Graboids only to be stopped by government agents who had been called in by Nancy for help. However, instead of helping, the agents banned any Graboid hunting, declaring Graboids a protected and endangered species. Their intention was to capture a live Graboid despite Burt's insistence that such a thing was impossible. They also planned to use eminent domain to force the Perfection residents to leave if they couldn't safely capture at least one Graboid. That night, a Graboid later named El Blanco became attracted to Burt's gun fire and visited his property, but didn't cross his property line so Burt couldn't shoot him. The government agents had no luck in hunting a Graboid and Jack was able to make a deal with them: in exchange for Burt helping them capture a live Graboid, he would be allowed to kill the other two. Burt reluctantly agreed to the deal and set out with Jack to catch a Graboid.
Out in the desert, Burt set up a chain with cans attached to his truck to attract a Graboids attention at which point he intended to have it swallow an RC truck with a bag of tranquilizer which would knock it out and allow the government team to capture it. However, as they were preparing, land developer Melvin Plugg arrived to try to convince Burt to sell his land so that he could build up the valley. As the two men argued, a Graboid was detected coming their way on Burt's seismo monitors and he warned the other two men to be quiet. Melvin, a former resident and survivor of the first Graboid incursion wouldn't shut up in his shock at first, but eventually did. Then his pager went off and he threw it at Burt's feet before Burt threw it far away. A Graboid ate it and came after Burt as Melvin fled in terror. While Jack got to safety on Burt's truck, Burt got stuck in an old metal barrel and was swallowed by the Graboid. As Jack mourned Burt's apparent death, Burt contacted him over the radio, revealing he was alive and ordering Jack to lead the Graboid through Burt's front gate. Confused, Jack did as he was told, using Burt's truck to lure the Graboid through the front gate of Burt's house. As a precaution incase the Graboids ever came back, Burt had encased his perimeter with box of solid concrete. Following Jack, the Graboid rammed itself head-first into the box, killing it. Jack quickly dug up the Graboid and cut it open with a chainsaw, rescuing Burt as Jodi Chang came to check on them after hearing of the attack from Melvin. While all of this was going on, Dr. Andrew Merliss came back to town with the news that he found two of the Graboid eggshells from their hatching, thus proving that Graboids come from eggs. He also learned that the Graboids lay dormant for over 300 years.
The next day, Burt, Jack, Miguel and Jodi continue their hunt for the Graboids while the government team do their own hunt. Burt grows concerned when he can only find one Graboid on his seismo monitor and finds out that the government team was chasing a Graboid instead of the other way around. At that moment, Doctor Merliss stumbles up covered in CO2 from a fire extinguisher he was carrying. Merliss explains that the team found the Graboid they were chasing only to discover that it had metamorphosed into Shriekers. The other members of the team were killed, but Merliss managed to escape by coating himself in CO2 from the fire extinguisher. However, he was still mortally wounded and dies after warning them of the Shrieker threat. Burt contacts Nancy and Mindy who are holed up on the roof of Chang's Market and tells them to get under some kind of cover because there are now Shriekers. Nancy and Mindy ultimately protect themselves by getting a cardboard box onto the roof and climbing into it. Burt uses infrared satellite tracking to locate the Shriekers, determining there are now seven of them. The four take off and when they get closer, check again to determine that there are now eight Shriekers but they are trapped in a box canyon that has no way out. At that moment El Blanco, drawn by the engine noise of Jack's truck and Burt's ultrasonic watch, attacks, destroying the back axel on Jack's truck and stranding the group on the rocks for the night. The next morning, after seeing that there are still only eight Shriekers and they are still trapped in the canyon, Burt decides to risk running to his truck to get his radio in order to call Nancy and Mindy for a distraction. However, Miguel created a makeshift fishing pole which Burt is able to use to get to his radio safely. Burt calls Mindy who blasts loud rock music through the radio at his request. Burt throws the radio, causing El Blanco to go after it, allowing the group to rush to Burt's truck and grab weapons before Burt sends the truck off on its own. El Blanco follows the truck, freeing the group to continue their pursuit of the Shriekers. Reaching the canyon, Burt throws one of his explosives, but they only find dead Shrieker husks that look like the Shriekers shed them and evolved into something else. Worried by this new development, Burt takes the others to find his truck.
The search for the truck leads them to a cliff that the truck drove over and crashed, ultimately exploding from the fire reaching Burt's ammo. At that moment, they notice a creature behind a nearby fence, what would later come to be known as an Ass Blaster and realize that its what the Shriekers evolved into. The four quickly open fire on the Ass Blaster, killing it, but not before it slams Miguel off the cliff, killing him as well. In the creature's remains, they find a Graboid egg realizing that this evolution of the species is used to spread it further. They also realize they used all of their ammo killing the Ass Blaster. Using a mattress as protection from the Ass Blasters' heat-seeking abilities, they follow a ridge back to Burt's house where they are safe from El Blanco and they try to plan their next move and contact Nancy and Mindy.
At the same time, after the discovery of the Ass Blasters, Burt and Jodi call Nancy and Mindy to warn them of the new aerial threat, but too late as one Ass Blaster attacks the two and chases them into the store. Heating up some food in the microwave, Mindy creates a distraction that allows the two to flee into the store's meat locker where they are safe. To their surprise, when the Ass Blaster eats "half the food in the store" it goes into a food coma instead of multiplying and they are able to capture it.
At Burt's house, an Ass Blaster breaks through the roof and into Burt's basement, forcing the group to flee into his safe room without any guns. While they are safe in the room, the Ass Blaster begins to burn through the door and the three believe that if it does and eats all of the food Burt has stored in there, it will multiply exponentially like the Shriekers, unaware of the new development regarding what happens when an Ass Blaster eats enough food. The group uses Burt's escape tunnel to get out, but not before Burt leaves a five-gallon container of fuel in front of the door for the Ass Blaster to detonate. The explosion kills the Ass Blaster and sets off a chain reaction of explosions that destroy Burt's house. While the three believe the threat to be over, they are contacted by Nancy who informs them of how feeding the Ass Blaster would've ended their problem. Burt is left horrified by the fact that he blew up his home for nothing and they spot four more Ass Blasters drawn by the fire. Realizing they need a place to hide, Jack spots the local junkyard and Burt's boat. Using the boat and a tarp to keep themselves safe from detection, they make their way to the junkyard.
Reaching the junkyard, they flee an Ass Blaster that spots them. Hiding they realize its in a perfect position for them to crush it with a refrigerator which they do, apparently killing it. While they celebrate their victory, they notice that the other four Ass Blasters have seen them and quickly flee into an outhouse where they won't be safe for long. Discussing their options, Jack comes up with the idea of creating a potato gun from the stuff in the junkyard to shoot flaming arrows and ignite the flammable chemicals in the Ass Blasters bodies to kill them. The three leave the outhouse after making sure its safe and split up to search for materials for their weapon, including moonshine from Nestor's old trailer. While searching, Jodi comes into contact with another Ass Blaster and lures it into a shed with gas cans in it. Spilling gas, Jodi escapes out a window and locks the Ass Blaster in. To escape, the Ass Blaster tries blast the door open and ignites the gas, blowing the building up and killing it. Having gathered what they need for their weapon, the three gather at an old mobile home and put the weapon together.
Shortly after the weapon is completed, an Ass Blaster is sighted. Loading a shot, Burt targets the Ass Blaster as it comes in and has Jodi fire. The flaming arrow hits the Ass Blaster in its belly and ignites the chemicals inside, blowing it up. As they reload, a second Ass Blaster lands on the mobile home roof and attacks Burt through a skylight, somewhat hindered by the small size of the skylight. Seeing an opportunity, Jack hefts Jodi through another skylight and she shoots the Ass Blaster while its distracted with Burt. The Ass Blaster falls off the roof and explodes. The group spots a final Ass Blaster landing nearby and fire at it, but the Ass Blaster learns from the mistakes of its comrades and dodges the shot. Before they can reload, the Ass Blaster attacks the mobile home directly and the three struggle to fight it off. Finally, Burt wraps one of their makeshift arrows in a fuse, lights it and stabs it into the Ass Blaster's side. As the three humans take cover in the bathroom, the fuse reaches the inside of the Ass Blaster and ignites its chemicals, blowing it up.
With all of the Ass Blasters apparently dealt with, the three believe the threat to be over only for El Blanco to attack them. Burt finally realizes that the Graboid is attracted to his ultrasonic watch, but before he can remove and dispose of it, a hit on the mobile home knocks him outside where he gets trapped on the springs of a mattress. As Jodi struggles to cut Burt free, Jack takes the watch and climbs on top of a nearby truck to distract El Blanco. However, the Ass Blaster they had pinned under the refrigerator proves to not be dead but just stunned and comes after them too. While Jodi prepares to try to defend Burt with a shovel, Jack gets an idea and wraps Burt's watch up in the duct tape Mindy used to fix his pants. Jack then throws the watch onto the Ass Blaster just before it can reach Burt. Attracted by the noise of the watch, El Blanco consumes the Ass Blaster before it can reach Burt, killing it. El Blanco then retreats having gotten the watch that had drawn it to Burt in the first place. With the Ass Blaster dead and El Blanco gone, Jack and Jodi are able to free Burt and they leave the junkyard.
Afterwards, Nancy and Mindy sell their captured Ass Blaster to Sigmund and Ray so Mindy can go to college despite Burt's insistence that they kill it. Rather than killing El Blanco who is sterile and thus cannot become Shriekers and eventually Ass Blasters, the townsfolk decide to spare his life and live alongside him in peace, setting up detection systems so they can know when he's around and be safe living with a Graboid in the valley. This is to ensure Perfection Valley is not built up as El Blanco's presence and status as an endangered animal prevents land developers from expanding in the valley. Burt explains this to Melvin Plugg before leaving him trapped on top of a rock with El Blanco circling him.