The film opens with Morticia (voice of Charlize Theron) on her wedding night to Gomez Addams (voice of Oscar Isaac). The ceremony is ruined by an angry mob of people who see the Addams family as freaks. As Gomez tries to lead them away, the mob burns a bridge that they would escape on. Not going down easily, Gomez teams up with his brother Fester (voice of Nick Kroll) and their mother, Grandmama (voice of Bette Midler), to fight off the mob before escaping. Gomez and Morticia lament that other people will not accept them, so they decide to get away to somewhere so horrible that nobody else would be caught dead in: New Jersey.
Gomez and Morticia make their way into the new state along with the disembodied hand Thing, but they hit something on the road. It turns out to be a large man from an insane asylum, Lurch (voice of Conrad Vernon). Gomez and Morticia spot the asylum on top of a hill and make their way up to find it abandoned and in a state of decay and squalor, along with a booming voice ordering them to "GEEEEEEEEEEEET OOOOOOOOOOOOOOOUUUUUUT!" The couple decides that place is perfect for their home. Thing and Lurch even play the family's theme on the piano.
Thirteen years later, Gomez and Morticia live in their cheerfully macabre home with their children, Wednesday (voice of Chloe Grace Moretz) and Pugsley (voice of Finn Wolfhard) Morticia has their living tree Ichabod wake the children. Wednesday is already bored until she hears a ringing sound from beyond the gates of their home. It is a young girl, Parker (voice of Elsie Fisher), ringing the bell on her bike. Wednesday responds by clanging on the gate, but Parker is spooked and she flees. Meanwhile, Pugsley tries to sneak up on Gomez with missiles and explosives that he made, but Gomez is too fast for him. Gomez wants Pugsley to get ready for his Mazurka, a long time Addams tradition for when they come of age, but Gomez isn't too confident in Pugsley's methods and prefers that he stick to tradition.
During a family meal, Gomez and Morticia make preparations for the rest of their family's arrival for the Mazurka. Wednesday questions what is beyond the gate, but Morticia isn't keen on letting her daughter know what's out there. Fester then crashes into the room after Morticia throws one of Pugsley's explosives out the window.
We meet reality show host Margaux Needler (voice of Allison Janney), who stars in her own home makeover program and is responsible for designing the town of Assimilation, which prides itself on being a perfect town. After a taping of the show, Margaux is approached by Parker, who is her daughter, as she claims to have heard something weird from up on the hill, but Margaux frequently neglects her daughter and forces her to act the way she wants her to. Parker rides her bike away, which causes a balloon to float up toward the Addams mansion.
Wednesday offers to help Pugsley prepare for his Mazurka, but she really just wants to bury him alive. She then spots the balloon coming down, along with the confetti from Margaux's taping. The rest of the family notices as well. The fog surrounding their home then lifts, revealing Assimilation to the Addams family. They decide to take a trip into town together with their pet lion, Kitty Kat. Naturally, the townsfolk are creeped out by the Addamses as they try to make sense of the town. They see a group of school kids, including Parker, performing a song-and-dance number on why it's great to be like everyone else. Fester interrupts and runs everyone off by unleashing a swarm of bats. The family is then spotted by Margaux, who learns that they live on the dark and morbid house on the hill. She offers to come by in the morning to help fix the place up, which Gomez and Morticia agree to.
The next day, Margaux arrives with her assistant Glenn (voice of Titus Burgess), camerawoman Denise (voice of Aimee Garcia), and mic guy Mitch (voice of Scott Underwood) to the Addams home. Parker tries walking inside too but gets shut out. She ends up meeting Wednesday, who is firing her crossbow at Fester. Both Wednesday and Parker are bored with their lives until Parker mentions her school to Wednesday, who takes an interest in seeing this part of the town. In the house, Margaux's crew is freaked out by the way the Addams family lives, but Margaux finds all the spots she wishes to fix...which is pretty much everything. Gomez and Morticia think she is already done and they thank her for the job. Glenn and Denise run away after Mitch disappears and they are too scared to keep going. Margaux tells Gomez she would like to fix his home since there are other houses in Assimilation that she is trying to sell, but when he suggests that his extended family would like to move there, Margaux becomes determined to do something about the Addams mansion at any cost.
Wednesday asks her parents if it is okay for her to go to school with Parker. Morticia is reluctant, but Gomez thinks it's a good idea. When she gets there, she finds Parker with her only other friends, twins Layla and Kayla (voice of Pom Klementieff). Parker is picked on by mean girl Bethany (voice of Chelsea Frei), who stuffs a moldy sandwich and some kid's soda in her backpack. Wednesday then manages to intimidate Bethany with a threat. In class, the students are set to dissect frogs. Wednesday instead builds a contraption that brings all the frog to life like zombies, and they proceed to attack Bethany and cause all the kids and teachers, except for Parker, Layla and Kayla, to run out. Parker thinks Wednesday is awesome for this, and the two become friends.
Grandmama arrives as Wednesday comes home with a pink unicorn beret in her hair, which frightens Morticia. She tries to handle the situation with her daughter, but is clearly unapproving of Wednesday's choices.
Wednesday goes to Parker's house where they both lament how their mothers want them to be the way they are and not how they choose to define themselves. Parker then dyes her hair black and adopts a goth look while Wednesday wears bright colors. As expected, their mothers are mortified. Morticia consults her deceased mother and father, Bill and Mary (Martin Short and Catherine O'Hara), through a seance. They assure her that Wednesday is just exploring right now and will eventually come back to her senses.
Gomez and Fester try to help Pugsley prepare for his Mazurka by utilizing swordplay, which is how both brothers passed their Mazurkas. Pugsley turns out to not be very good at it, and he is discouraged by Gomez's obvious lack of confidence in his skills.
Following an argument with Morticia, Wednesday confides in Pugsley that she is running away. However, Pugsley blabs to his mom where his sister went anyway. Wednesday goes to Parker's house, where Parker is looking for her phone. Wednesday suggests it's in Margaux's crafting room, which Parker says they are not allowed in. They go in anyway and discover a room with cameras, as Margaux has hidden cameras in all the homes in Assimilation. Margaux finds the girls in there and locks them in the attic, but Wednesday manages to pick the lock.
The extended Addams family starts making their way into Assimilation, creeping out all the townsfolk. With her season finale approaching, Margaux rounds up the townspeople as an angry mob by spreading rumors about the Addamses, and they start making their way to the mansion. Up there, the family greets old relatives like Cousin It (voice of Snoop Dogg) and Great Auntie Sloom (voice of Jenifer Lewis), Grandmama's sister. Auntie Sloom seems most keen on seeing how Pugsley performs his Mazurka. The ceremony begins with Pugsley doing a reading (which is just a howl and a scream) before getting ready for the sword duel. He grows facial hair like his father, but as he engages in the sword-fight, Pugsley fails and falls on his face. As he sees the disappointment in his son's eyes, Gomez realizes he was wrong and that he should have let Pugsley handle it his own way, with his explosives. Suddenly, a boulder flies in through the house. Margaux has a catapult set up to start hurling more boulders at the Addams house to destroy it and kill the family. The family huddles together for protection, but they are saved from the roof caving in as Wednesday leads Ichabod to save the family. Pugsley then uses his explosives to destroy the catapult.
The Addamses gather outside in front of the townspeople, who all see that they are harmless and only a loving family. Margaux is still trying to turn the people against the Addamses, but Wednesday and Parker reveal to the townspeople the facts about her hidden cameras. As she starts ranting to them, Parker informs her that she has been recording her mom live, and now all her former fans see who Margaux really is. Not long after, Glenn informs her that the show is canceled. The townspeople apologize to the Addamses, now accepting them for who they are.
The townspeople help rebuild the mansion, while Margaux is now with Fester since he fancied her, and now they are partners in selling the homes in Assimilation to the extended Addams family. The whole family then gathers for a group photo, which transitions into the original theme song playing them out.