A mosquito flies away from an abandoned government facility in Florida and towards the campus of Tallahassee State College, home of the Fighting Manatees. It lands on a sign as Chad and Boone walk by, talking about their dates that night. Boone objectifies Chad's date, despite having his own date. The two frat boys run into Beth and Wiki. Chad talks to Beth, who tolerates him. She ignores Boone. Boone makes fun of Wiki, but she runs intellectual circles around him.
The mosquito flies through the woods and comes upon a nuclear research facility. The mosquito flies into the building, unnoticed.
Later, a mosquito flies into the second-story apartment of Beth and Wiki. It lands on Beth's neck. She swats it and goes back to playing her video game. Wiki plays with her and their apartment contains every major game system and tons of games. They are listening to Coolio and debating the finer points of "Cabin in the Woods." Wiki wins the game and someone knocks on the front door and Wiki tosses her controller into a PBR mirror, shattering it.
On the other side of campus, a mosquito flies into Chad and Boone's apartment and lands on the bathroom mirror. Compared to Beth and Wiki's apartment, Chad and Boone's is a palace. Filled with rich toys that are unused. The frat boys get ready to go out, standing in front of twin mirrors. Boone takes off his towel, leaving him naked, and snaps the towel to kill the mosquito. They comb their already perfect hair and discuss what's happening tonight. Chad makes a joke about Boone and Boone gets really angry about it. Chad tells him to calm down, it's just a joke. Boone doesn't like jokes.
Back at Beth and Wiki's apartment, their drug dealer Snorkel has arrived. He delivers two ounces of the best weed in town. He tells them he gets his weed from Snoop Dogg and they start smoking. Snorkel flirts with Beth, but she's not interested. Snorkel asks to use their restroom, but it's broken. They reminisce a bit about old times when someone knocks at the door.
At Chad and Boone's apartment, Boone asks what Chad thinks about Wiki. Chad says he doesn't. It's clear Boone does. Chad reminds him that Wiki hates him. Boone thinks she's playing hard to get. Chad reminds Boone that he already has a girlfriend and says Boone is being gross. Someone knocks on the door. Boone drops his shades and accidentally breaks them. It's another friend, Trog. Chad hates him, but Boone thinks he's awesome. Chad isn't really into the fraternity, he just wants a job at a cushy law firm. Boone wants to get into Skull & Bones. Trog comes in and it's time to party.
Beth invites Don, their landlord, into the apartment. He's excited that they're listening to old school Coolio, who happens to be Don's cousin. Don's here to pick up the rent. Beth reminds him that they legally don't have to pay until he gets the place up to code. Don starts to get aggressive, but Snorkel reveals a .357 Magnum. Don leaves, saying he's going to get his cousin (not Coolio) to fix Beth and Wiki's broken bathroom. Snorkel leaves out the back door and a mosquito follows him.
Snorkel uses the flashlight on his phone to make his way to the porta-potty out back. The backyard is so overgrown it's almost a forest. He goes inside the porta-potty and takes a seat. A mosquito flies in and lands on his neck. Snorkel swats it and says somebody has to do something about these mosquitos.
Outside the Delta Sorority House, Sheila and Bitsy wait for Chad and Boone, who are very late. They get tired of waiting and go inside. A mosquito tries to follow them in and land on Bitsy, but the door crushes it just in time.
At the Zeta Fraternity House, Chad and Boone are participating in an initiation ritual and have to wrestle each other in creamed corn. Trog leads the festivities and the entire fraternity watches on, drinking and cheering.
Beth and Wiki are bored and decide to play Pokemon Go. Snorkel was sleeping on the couch, but they kick him out. He hits on Beth again, but she's a lesbian.
At the Zeta fraternity house, Trog tells the pledges that they have to go on a top secret mission. Chad and Boone are teamed up and they have to succeed at the mission or they are out as pledges. Chad insults Trog, but the older frat boy doesn't hear it. A mosquito lands on Trog's forehead and he smacks himself so hard trying to kill it he knocks himself down.
Beth and Wiki walk through a forest near the college, playing Pokemon Go. Wiki smokes a joint as she plays. Beth sees something deeper in the forest and goes to look at it. Wiki is weirded out but follows. They emerge to see the Smithers Nuclear Research Facility. They watch Chad and Boone cut a hole in the fence and sneak into the facility.
Chad and Boone walk through the facility, Boone drinking beer as he goes. They wander through the halls with light security and old or broken security cameras. A mosquito follows them down the hall. Using a keycard given to them by the frat, Chad sneaks into a room with glowing green rods of nuclear fuel. Using the facility's tech, they steal one of the nuclear rods. As they are putting it into a special case, the mosquito lands on the nuclear rod. It takes a bite and starts glowing a nuclear green. It flies and lands on the back of Boone's neck. It bites him and he swats it. Thinking it dead, they leave. But the nuclear mosquito continues to suck from Boone's blood.
As they go back outside, they run into Beth and Wiki. Chad says they're doing a frat prank. Beth jokes about him trying to get into his dad's frat, but Chad says he has to do it to get the job. His dad really wants him to. Wiki notices that Boone is starting to look sick. An alarm goes off inside the building and the two duos split up and run away.
Chad drives them to pick up Bitsy and Sheila, but Boone says he really doesn't fell good. Chad agrees that he looks very bad. Boone says his neck is throbbing and asks Chad to check it out. Boone turns to reveal the glowing green mosquito is still attached to his neck and it has now grown to the size of a softball and is sucking Boone's blood. Chad freaks out and crashes into a light post. The car bursts into fire, but it's not going to explode.
The mosquito, now the size of a dog, suck the life out of Boone and he deflates like a life raft. Chad screams and scrambles to get out of the car and away from the Beersquito. Police and EMS are on the way. Chad makes it out of the car. The Beersquito rips through the roof of the car and runs towards the arriving cops. They leap out of their cars and tell Chad to drop to the ground. He does and the Beersquito attacks the cops. They shoot at it, but the bullets do nothing. The Beersquito blasts beer from its proboscis and disintegrates the cop car. Some of the cops keep shooting at it, some start to run. The Beersquito impales one of the cops and sucks him drive. Chad runs into the forest. The tail of the Beersquito bursts open and dozens of larval Beersquitos burst out. They devour one of the cops. The Beersquito chases the fleeing cops while some of the larval Beersquitos chase Chad. Others head towards the campus of Tallahassee State College and in the direction of fraternity and sorority houses.
Beth and Wiki are walking through campus and come across the Kappa fraternity house. The door man invites them in for the house's 10th Anniversary Party. Featuring Coolio. Beth and Wiki go inside and he doorman sees Chad run past the front door. The doorman ignores Chad and goes inside. The larval Beersquitos appear. Some follow Chad, some head towards the Kappa house. One stops and hardens into a cocoon. Other cocoons can be seen in the background.
Larval Beersquitos arrive at the Delta sorority house and scale the building towards an open window.
Inside the Delta house's dining hall, the room is empty and set up for the 17th Annual Delta House Dodgeball Piefight. The sorority girls are divided up into two teams of 10. Kristy With a K leads one team. On the other team are Sheila and Bitsy. Larval Beersquitos slither into some of the pies on the table. The teams grab pies and prepare to start the fight, not knowing which pies have larval Beersquitos. The pie fight begins.
Beth and Wiki go into the Kappa house, which is preparing for a step show and has a packed crowd. Wiki meets Coolio and they hit it off when she compliments "Too Hot" instead of a more popular song like "Gangsta's Paradise." They watch the step show as two teams perform. The crowd goes crazy. Wiki and Coolio kiss.
Outside, the cocoons of the larval Beersquitos begin to crack open, releasing smoke and revealing a glowing green light from within. Emerging from the cocoons are smaller, flying versions of the Beersquito. They blast beer at the front door and melt it. More flying Beersquitos are heard in the distance.
Outside the Zeta house, Chad runs up on several brothers talking outside. He warns them and runs inside. Moments later, he has told them the story of the Beersquitos killing Boone, but they are skeptical. Someone knocks at the door and scares them. Chad opens the door and it's a beaten and battered Boone. The frat bros make fun of Chad for lying about Boone. The Beersquito sucks what's left of Boone into its proboscis and the smaller flying Beersquitos arrive. Chad runs away while everyone stares in shock and fear. The Beersquitos attack, with more of the larval ones arriving. Trog and a few of the other frat boys escape, but the rest are eaten up by the Beersquitos.
At the Delta house, the pie fight continues. Buffy throws a pie at Chrissy and it contains a larval Beersquitos. The party descends into chaos as more and more Beersquitos reveal themselves. Sheila very acrobatically makes her way towards the window with her training for American Ninja Warrior. She leaps out the window and runs off while many of the other women are being killed by the Beersquitos.
After the step show, Beth and Wiki join Coolio for drinks. He continues to flirt with Wiki and she's totally into it. Beth flirts with a woman in Coolio's entourage, Esmeralda. Coolio performs "Too Hot." As he does the chorus, a loud buzzing sound begins to dominate the room and he cuts the performance short. That's when the Beersquitos arrive and attack. Chaos ensues. The doorman shows Coolio a secret exit and they exit, with Coolio, Beth and Wiki going one way and the others going another way.
Outside, the giant Beersquito destroys the Zeta house.
Near the front of the campus, Beth, Wiki and Coolio arrive at the same time that a sheriff's car arrives. Sheila arrives from Delta house. Don arrives from a strip club. Lastly, Chad and Trog arrive. Chad grabs Sheila and kisses her. Another sheriff's vehicle shows up and out steps Sheriff Danny Glover (not that one).
People run to and fro, the entire campus is in a panic. One of the smaller Beersquitos flies towards the sheriff and he shoots it in the face, killing it. Glover notes that they can be killed, but Beth points out none of them have weapons. Trog assumes the Black people have guns, but he's shut down. The sheriff tells them to search nearby buildings for weapons and meet back in five minutes.
Trog thinks that if he drinks a lot of beer, he'll be immune to the Beersquitos. He runs towards the Beersquitoes and they instantly melt him. Wiki decides that the big ones are called Beersquitos and the little ones are called Squeerbitos. They come back with "weapons" that are actually various sporting goods: a bat, a javelin, a bow and arrows, golf clubs. Coolio found two samurai swords and he knows how to use them. Other students have crowbars and broken table legs and pool cues.
Dozens of flying Beersquitos come at them. They are surprisingly effective and only a few no-named students are killed. Coolio is VERY effective with the swords. They are all pretty effective, but more and more Beersquitos and Squeerbitos and larval Beersquitos arrive. A loud buzz informs them that the prime Beersquito, the original, is coming. The sheriff tells them to have everyone meet at the cafeteria.
On the way, they all gather in an alley while chaos continues to reign. Wiki and Beth light up. Don joins them and takes the joint. After he smokes, he complains about the quality and starts to brag about the shit he used to grow. That's when a Beersquito shoves its proboscis through the back of Don's head and out his mouth, killing him. It turns on Chad and he coughs weed into the Beersquito's face. It coughs and flies away drunkenly. Then it explodes. Chad repeats it and Glover concludes that weed kills the Beersquitos. It turns out that Coolio is NOT Don's cousin. They continue towards the cafeteria.
At his apartment, Snorkel is watching porn when the doorbell rings. He opens the door to find Harold, Kumar and Neil Patrick Harris. They're here to buy weed. They ask where Snorkel gets his shit and, once again, he claims he gets it from Snoop Dogg. He goes to light up a bong to show them how good it is when they realize a Beersquito is attached to the bong and sucks his entire face into the bong, killing him. The others run away and NPH grabs Snorkel's weed as they go.
Everyone meets near the Tallahassee State College cafeteria. Glover tells them all he has no idea what to do, this is all above his pay grade. Sheila and Chad are pessimistic. Glover reveals that a federal agent is being sent to take over the situation. He arrives. The Federale. He tells them that they have six hours to figure the situation out or Operation Gigli will begin. It's a scorched earth campaign that will destroy the town with nukes.
Beth leads everyone to the Nuclear Research Facility and they meet with Dr. Theophilus Rex, the director. He already knows why they are there. He's right. He reveals that he's been working on a weapon to fight the Beersquitos. Glover asks if it is a giant bong and Rex replies that it's a giant nuclear bong. And he's already made one and he gives it to them.
They go to Snorkel's apartment to get weed for the giant nuclear bong. They knock on his door, but there is no answer. The door is open, though, so they go inside and look for him, but they find his body. Not only that, the weed is gone. Beth says that Snorkel always bragged that his source was Snoop Dogg, which they agree is silly. Except for Glover, who says that Snoop Dogg actually has a mansion on the outskirts of town.
They arrive at Snoop's mansion and Coolio knows him, so he let's them in. Coolio tells Snoop it's an emergency, but Snoop is finishing up a song. He and Coolio perform "Puffeye the Smoker Man" while everybody celebrates and dances along. After the song, they tell Snoop that they need all his weed to defeat the Beersquitos and save the world. He's in.
Breaking the fourth wall, a Corporate Spokesperson interrupts the movie to tell viewers that the heroes go ahead and crop dust all the Beersquitos with weed, but that the filmmakers don't really have the money, so it's a no go. He leaves and we cut back to Snoop getting everybody high. They remember what they were supposed to be doing and meet up with the Federale.
The Federale tells them that the Wobbles are playing at the Civic Center. Apparently Beersquitos and Squeerbitos love the Australian accent. All of them are going to converge on the Wobbles concert. The Federale says that the 17th Beersquito outbreak was stopped in Katmandu in 1982 by Men at Work. The Federale says the Beersquitos will converge on the civic center and they can use the giant nuclear bong to kill them all while they're in one place. They head towards the civic center.
When they arrive, the Beersquitos surround the civic center. The Federale relieves local police of duty and hands things over to Glover. Glover hands out weed guns, which will be used to herd all the monsters inside the building. They split up and several minutes later, they've herded all the Beersquitos inside. The audience inside is protected from the Beersquitos. As Beth and Wiki question the plan, the Federale says it's already done. They've already used the giant nuclear bong and the Beersquitos are dead and everyone inside is safe.
Later, Men in Black lead the kids and families from the Wobbles show onto various buses. On the buses, their minds are wiped.
The main Beersquito is still alive and attacks them. Everyone with a gun turns and shoots it. It crashes to the ground. It rears its head again and they shoot it again. They poke it with a stick, it roars to life and they shoot it again. The Beersquito comes to life one more time and kills the Federale as he's telling his superiors a code. The Beersquito crushes the walkie talkie and no one knows if the message to call off Operation Gigli went through. They shoot the Beersquito dead. Again.
A jet flies overhead, but doesn't drop any bombs. The Beersquito rears its head one more time and they shoot it dead. Wiki and Beth high five and the credits roll. Puffeye the Smoker Man plays over the credits. After the credits, the Beersquito raises its head again and the cops gun it down one last time.