In 1897, Dracula (Adam Sandler) was taking a train ride with his friends, Frank (Kevin James), Griffin (David Spade), Murray (Keegan-Michael Key), and Wayne (Steve Buscemi), all of them disguised in women's dresses. Suddenly, Abraham Van Helsing (Jim Gaffigan) burst in and announced that there were monsters on the train. He held a match under Frank's nose, making him freak out. All the monsters ran and jumped onto the roof of the train, with Abraham in pursuit. Reaching the last car, Dracula pushed the rest of the monsters off to safety before Abraham cornered him. Dracula turned into a mouse just as the train entered a tunnel, and Abraham got smacked. With the train exiting the tunnel, Dracula turned into a bat and flew off, with Abraham giving chase in a biplane. Dracula kept dodging his attacks, always making him crash in painful ways. Finally, Dracula made Abraham fall into the ocean.
In the present day, Dracula is hosting a monster wedding at the Hotel Transylvania. The groom is ready, but the bride is still in her room. Mavis (Selena Gomez) is with her, getting her over the jitters. She tells the bride that you only zing once in your life, and if she zinged when she first saw her fiancee, then she has nothing to worry about. Reassured, she goes down and joins the ceremony. After the wedding vows are done, Tinkles, a giant dog, burst into the room, being ridden by Dennis (Asher Blinkoff) and Winnie (Sadie Sandler). Dracula orders Tinkles to sit, and leads him out on a leash. Later, Johnny (Andy Samberg) is DJing the reception and everyone is dancing, except Dracula, since he has nobody to dance with. Suddenly, Frank's cousin grabs Dracula and starts dancing with him. He zaps the DJ table, causing a fast song to start playing, then hides behind Bigfoot's leg. Frank asks him if he liked her, and he says that he didn't zing with her.
Alone in the attic, Dracula tries to use his phone to look for a date, but it keeps mishearing what he wants. Mavis walks past and hears him through the door as he uses the ZINGR app to look at pictures. Unable to swipe correctly with his long fingers, he accidentally connects with a witch when Mavis pokes her head in. He cuts off the call, and Mavis says he's been working too hard. She goes to her room and cuddles with Johnny and the kids, when a commercial comes on the TV, advertising a monster vacation.
In a rickety old plane, Dracula, Mavis, Johnny, Frank and Eunice (Fran Drescher), Wayne and Wanda (Molly Shannon) and their pups, Griffin, Blobby (Genndy Tartakovsky) and Vlad (Mel Brooks) are all riding toward the Bermuda Triangle. Dennis and Winnie had secretly stowed Tinkles in the luggage compartment. The plane crash lands and everyone gets out and makes their way to an aircraft carrier. The crew leader, Stan the fish man (Chris Parnell) greets them, and the cruise sets off. Griffin, traveling with his invisible girlfriend, Crystal (Chrissy Teigen), sees Dracula looking unenthusiastic. The ship's captain, Ericka (Kathryn Hahn) greets everyone in multiple languages, and Dracula's face freezes. She walks up to him and tries to talk, but he can only speak gibberish. His friends try to snap him back, and he tells them that when he saw her, he zinged.
Later that night, the monsters are dancing, swimming and doing other fun activities. Blobby, feeling seasick, changes colors and vomits, producing a Baby Blobby (Genndy Tartakovsky) who hugs him. Wayne and Wanda see a room labeled Kid's Club, and they happily drop off the pups for the day. In her stateroom, Ericka greets her great-grandfather, Abraham Van Helsing, who is now in a wheelchair. She tells him that he was right, monsters are disgusting, and she wanted to kill Dracula the first time she talked to him. He tells her to be patient, and doing research, he read about the ultimate device, one that destroyed the city of Atlantis. He tells her to lure them all to Atlantis, and he'll use the machine to kill them all.
Still determined to kill Dracula, Ericka hides and takes many shots at him, but he always manages to just avoid her blows, not even realizing what's happening. Meeting his friends, he tells them that he always thought you could only zing once in your life, and he already had with his late wife, Martha. They all jump in the pool and start a game of volleyball when Ericka's voice comes on the speakers and tells them they've arrived at their first destination, the underwater volcano. They all grab scuba gear and jump into the volcano. Ericka fills a vessel with wooden stakes and chases after the group. Dracula hypnotizes a shark, and he and Dennis ride it around, with Ericka still secretly following. She tries to shoot wooden harpoons at him, but keeps just missing. Seeing the vessel, Dracula grabs the tail end and poses for a picture from Mavis. Panicked, Ericka launches herself out. Looking at the picture, Mavis sees what looks like human feet in the corner. Reaching the surface, Ericka sputters and gets back on the ship. Frank, Murray and Griffin are also on board getting snacks, when they hear Ericka muttering. Keeping themselves hidden, they hear her vow that she's going to get Dracula. Misunderstanding her, they think she's in love with him too.
With everyone back on the ship, the guys run up to Dracula, and then see that Mavis is with him. Fearing her reaction to hearing about Ericka, they lead him away, and then tell him that Ericka likes him. Just then, Ericka walks up and listens in as they ask if he's going to ask her out. At first, she's disgusted, but then she realizes she has an opportunity. Pretending she just walked up, she greets him and says she'd love to go on a date. Arriving at the next destination, the deserted island, Dracula volunteers to take Dennis, so that Johnny and Mavis can enjoy themselves. At a restaurant, Mavis asks Johnny if he noticed Dracula's been acting weird, and he tells her that Dracula has a crush on the captain. Taken by surprise, Mavis says that she never imagined him with anyone except her mom, but she does want him to be happy. In the cantina, Ericka orders guacamole for Dracula, then secretly dumps garlic oil on it. She takes a chip, dunks it in the guacamole and feeds it to him. He swallows, and then his stomach starts to rumble. He asks if there was garlic in the food, and she lies and says she doesn't know. She asks if that's deadly for him, but he says that it only makes him gassy. He tells her he's nervous, since he hasn't been on a date since his wife died. He explains that he built the hotel so that he and Mavis could have a safe place to live. Touched by his obvious love for his daughter, she replies that she never knew her mother or father, and she was raised by her great-grandfather. Growing up on the ship, she tells him that it was always expected that she'd be captain one day. He says it's important to honor the past, but to make your own future. Thinking about that, she realizes that she doesn't want to be on the ship forever.
Mavis and Johnny walk up to the table. Panicked, Ericka realizes she lost focus on her mission, and she quickly excuses herself. Mavis reminds Dracula that he was going to spend time with Dennis, and he hurries off to find him. Sitting down at the table, Mavis tells Johnny there's something she doesn't trust about Ericka. Johnny eats a chip with guacamole, then warns Mavis that it's loaded with garlic. Mavis realizes what Ericka is up to. Wayne and Wanda, still relieved to be pup-free, are running around the deck. Ericka hides from them, and is surprised to hear Abraham's voice coming from a vent. He tells her he knows she's been trying to kill Dracula, and that it could blow the whole plan. Making another lap, Wayne and Wanda run up to them, and Abraham quickly puts tranquilizer darts in their necks, and they fall to the ground, unconscious.
Arriving at Atlantis, they all go into a casino. Eunice makes Frank promise not to gamble, since the last time he did, he lost an arm and a leg. Dracula asks the guys if they've seen Mavis, and he tells them that he's going to tell her about Ericka. Mavis and Johnny see Dracula on the floor, and she notices that he's following Ericka around. Suspicious, she tails after them, and Ericka goes into a hidden room. Arriving at a pool, she takes off her clothes, revealing a wet suit she was wearing underneath, and dives in. Dracula follows her, unseen, and she emerges at the ruins of a palace. At the end of a hallway is a strange glowing device, and she makes her way to it. She steps on a stone and sets off a booby trap, sending an ax flying toward her head. Dracula quickly grabs the ax and tosses it aside. She realizes that he's been following her, and he saved her life without thinking. She starts to think that everything she was told about monsters was wrong. He asks her what she's doing, and she lies and says that the device is an old family heirloom, and she wants to get it back. Taking another step, she sets off a second booby trap, and Dracula grabs another ax out of the air. Testing him, she skips forward, setting off all the traps, with him saving her every time. He ends up with axes, darts and arrows embedded all over his body. She grabs the device, causing the room to shake and crumble, and he flies her out just before she gets crushed.
Mavis catches up to them, and sees Dracula looking like a pincushion from the traps. Her eyes turn angry, and she levitates Ericka up. Dracula tells her to stop, then says that when he first saw her, he zinged. Stunned, Mavis drops Ericka, and she asks what a zing is. Dracula explains that it's a love at first sight for monsters. Feeling guilty, Ericka tells him that she can never be with a monster, and she runs off. Mavis hugs Dracula, and he sulks away.
Back on the ship, Murray shows off the tattoo he got last night, and Griffin and Crystal walk up, with her wearing a wedding ring on her invisible finger. Frank and Eunice arrive, and he has no arms, having lost them gambling. In her room, Ericka shows the device to Abraham, and then tells him that Dracula saved her life. She says the way he acted with Mavis was almost human, and he replies that monsters have no feelings, and they must fulfill the mission. The next day, Frank has replaced his arms with lobster claws from the seafood buffet. At a dance party, Mavis is still trying to process the fact that Dracula zinged with Ericka, and Johnny tells her that love makes them do crazy things. He reminds her that they were different species, but when they zinged, nothing could keep them apart. Realizing that Johnny was right, she runs up to talk to Dracula. She tells him that he has to tell Ericka how he feels, and he starts off to find her. Just then, the music stops, and Abraham's face comes on the monitors. He says he knows that Dracula recognizes him, and he holds up the device. Dracula says that it's just Ericka's heirloom, but Abraham reveals that Ericka retrieved it because she's his great-granddaughter. He shows them that it's a canister with sheet music. He plays the music on a piano, stirring a creature known as the Kraken.
With the Kraken swatting at the guests, Dracula flies toward Abraham, but is caught by the Kraken in midair. He tries to free himself by changing forms, but the Kraken maintains its grip. Ericka looks at him sadly. Trapped and growing weaker, Dracula submits to defeat. Mavis tries to save him, but the Kraken pins her down, and throws Dracula into the air toward his mouth. At the last second, Ericka jumps and bounces off Blobby, and she grabs Dracula out of the air. They land in water at the edge of the dance floor, and she holds him up and tells Abraham that he can't kill Dracula. She says monsters have families, and laugh and love just like people. She says she knows it because when she first saw Dracula, she zinged.
With renewed determination, Dracula starts to fight back against the Kraken. Johnny stops him and tells him that the only way to fight the ominous music that Abraham is playing is with happy music. He sets up his DJ equipment and plays "Good Vibrations." The Kraken starts to sway to the beat, until Abraham makes his music louder, causing the Kraken to resume the attack. Finding an even brighter song, Johnny plays "Don't Worry, Be Happy," and the Kraken starts swaying again. Abraham makes his music louder still, and Johnny realizes he needs the ultimate musical weapon, and starts playing "The Macarena." Soon, both the Kraken and Abraham are moving their arms to the music, unable to control themselves. Abraham falls off the DJ booth and toward the water, and Dracula turns into a bat and flies up to him, grabbing him before he hits. Dracula returns Abraham to the dance floor, and he asks why he had saved him. Dracula says that human or monster, we are all the same. Ericka runs up and hugs him, and Abraham sheepishly offers them all a full refund for the cruise. The wolf pups stampede around the deck, and everyone realizes they haven't seen Wayne and Wanda in a long time. Ericka takes them to the closet where she had hidden them, and Dracula zaps them back to life.
Back at the hotel, Dracula and Ericka sneak up to the roof, and she asks if he's going to suck her blood. He responds by getting down on one knee and opening a box with a spider-shaped ring with a red jewel. The ring claws its way onto her finger, and she tries to answer, but can only speak gibberish. Everyone else shows up and asks what her answer was. Recovering, she says yes, and everyone cheers. Tinkles happily runs in and tackles them both. A happy new chapter had begun at the Hotel Transylvania.