In 1996, teenager Alex Vreeke (Mason Guccione) receives the original (and cursed) Jumanji board game after his father finds it while jogging on a beach, but puts it aside, dismissively noting that nobody plays board games anymore, instead playing a video game involving motorcycles. Overnight, the game changes so that the box's contents are now a video game cartridge, but when Alex puts it in his console and turns it on, he vanishes.
Twenty years later, high school student Spencer Gilpin (Alex Wolff) is sent to detention for helping his former best friend, Anthony "Fridge" Johnson (Ser'Darius Blain), with his homework by writing Fridge's essays for him. They are joined by Bethany Walker (Madison Iseman), a beautiful girl who was caught talking on her phone during a quiz, and Martha Kaply (Morgan Turner), a socially awkward girl who objected to being made to participate in gym class. For detention, they are charged by Principal Bentley (Marc Evan Jackson) with removing the staples from discarded magazines in an old storage area, but Spencer discovers the console containing the Jumanji game and convinces the others to play it with him. They are unable to access one of the five-player options, a pilot, but once all four others have been selected, the game draws them all inside it.
Finding themselves in a jungle, all four are shaken to realize that they have become the avatars they chose for the game. Spencer finds himself turned into Dr. Smolder Bravestone (Dwayne Johnson), a muscular archaeologist. Fridge arrives into the game as Franklin "Moose" Finbar (Kevin Hart), an expert zoologist, but Fridge is upset that his avatar is a foot shorter than he normally is. Martha becomes Ruby Roundhouse (Karen Gillan), "killer of men". Bethany is now Dr. Shelly Oberon (Jack Black), a cartographer that Bethany mistook for a woman because the description read "curvy genius" (and she becomes horrified upon seeing her reflection). The four freak out as they realize they are in the game. Almost immediately, Bethany is suddenly eaten by a hippopotamus that emerges from the river, but she swiftly reappears after falling out of the sky.
Fleeing from a stampede of hippos, the group encounter Nigel (Rhys Darby), whose repetitive responses help Spencer identify him as an NPC (non-player character) who tells them that they have come to Jumanji (in the context of the game) in response to a letter Nigel wrote to Spencer's avatar. The letter explains that Nigel was part of an expedition by explorer John Hardin Van Pelt (Bobby Cannavale) to claim the legendary gem, the "Jaguar's Eye", removal of the gem from the large jaguar statue granting Van Pelt control over the animals of Jumanji. In order to complete the game, the players must return the gem to the jaguar statue and call out "Jumanji".
With those instructions given, the group are dropped off outside a forest, where it is revealed that Bethany alone can read the map Nigel gave them, the map directing them to the next stage of their quest. They are subsequently attacked by Van Pelt's men on motorbikes, but manage to escape by fleeing through the trees and jumping off a cliff into a river. After emerging from the river, Martha realizes that she has been shot, but returns to the group immediately after her avatar explodes. Examining a series of line tattoos on their forearms, which originally consisted of three bars where Martha and Bethany now only have two, Spencer realizes that these bars indicate the number of lives they have in the game, guessing that they will die for good, both in the game, and in the real world as well, once they lose all three lives.
While traveling to the bazaar where they will receive their next clue, an argument between Spencer and Fridge over Fridge's perception of Spencer's role in this problem results in Fridge pushing Spencer off a cliff, costing him one of his lives. In the bazaar, Fridge loses one of his lives when he eats cake - previously identified as one of his character's weaknesses - and explodes, drawing the attention of Van Pelt's minions. Fortunately, before they are attacked, they discover their next clue hidden in a basket containing a snake, which the team are able to acquire by pooling their skills and coming together, allowing Spencer to catch the snake while Fridge defangs it. When Van Pelt's forces attack, Spencer attempts to fight them off, but they are soon confronted by Van Pelt himself, only just escaping when another player uses a smoke grenade as a distraction and leads them to a secret passage.
The fifth playable character introduces himself as the pilot Jefferson "Seaplane" McDonough (Nick Jonas), who says his real name is Alex. He leads the gang away. Alex takes the four to a tree-house that once belonged to Alan Parrish (Robin Williams's character from the original movie). He makes margaritas for the gang, and Fridge gets drunk. Alex mentions that he has been stuck in the game for months, and he hasn't been able to get to the transportation shed to get himself out. Alex has used up two of his lives and been unable to progress further without the others due to his limited skills, but has identified the transport shed where they will acquire the means to move on. While Bethany teaches Martha in how to flirt to distract the guards, Alex's dated references lead Spencer and Fridge to realize that he is Alex Vreeke, Alex in turn, being shocked to learn that he has been trapped in the game for over twenty years. Although Alex suffers a panic attack, the team are able to gain access to the transport shed after Martha taps into her character's strength of dance combat, subsequently helping Alex recognize that they can complete the game by working together.
There is a brief panic when damage to the helicopter traps it in a canyon in front of a rampaging herd of white rhinoceros, but Spencer is able to repair the damage and help them ascend. Unfortunately, they lose the gem when it falls out of Fridge's backpack, but Spencer is able to reclaim the gem after using Fridge as a 'sacrifice' to draw the rhino herd's attention, subsequently ordering Alex to spin the helicopter in time to catch Fridge as he 'respawns'. Once they land, Alex is stung by a mosquito and begins to die due to his avatar's weakness, but Bethany saves him by giving him CPR, which passes one of her remaining lives to him. As they prepare for their next step, Spencer and Martha admit that they have feelings for each other in the real world, while Bethany begins to bond with Alex.
Making their way to the jaguar statue, they find themselves confronted by actual jaguar guards, which cost Spencer one of his lives when he attempts to take the gem along the path to the statue alone. With Fridge's support, Spencer implements a plan where Martha takes out Van Pelt's approaching minions while the other three provide a distraction for the jaguars, leaving Spencer to take one of the minion's motorbikes and continue to the statue. Van Pelt attempts to gain the advantage by taking Bethany hostage, but Fridge is able to drive the jaguar guards away by befriending an elephant, only for the players to lose the gem when it is thrown away. While the others distract Van Pelt's minions, Spencer takes the bike to the top of the statue while Martha retrieves the gem from a pit full of snakes, using her character's weakness to venom to sacrifice her second life and 'respawn' in a position where she can pass the gem to Spencer as she falls. With this action, Spencer places the gem in the statue and calls out "Jumanji!", ending the game and restoring the jungle to peace. With this victory, Nigel appears to congratulate the group, shaking their hands and returning them to the real world.
Back in the storage room, all four detention students have returned to their true forms, but are saddened to find that Alex is not among them. As they walk home, they witness the Vreeke household - which had fallen into disrepair as Alex's parents had no answer as to his fate - has been fully restored. As a car parks outside the house to release a family, the father sees the former players and confirms that he is Alex, who emerged from the game in 1996 and changed his history, also revealing that he named his eldest daughter after Bethany.
The following week at school, Spencer and Fridge are friends once again, and Bethany is making plans to go backpacking, while Spencer and Martha start dating. When they hear the drumbeats of Jumanji, they take the console out to the back of the school and Fridge drops a bowling ball onto it, each intending that this will end the game once and for all.
However, at the end of the end credits, Jumanji's menacing jungle drums play once again, suggesting the game still exists in some form to play another of its dangerous games.