NOTE: This spoiler was submitted by Jeremy

The film opens on the streets of New York where agents from TCRI (Techno Cosmic Research Institute) are hunting for mad scientist Baxter Stockman (Giancarlo Esposito), who has created his own mutant. Per orders from CEO Cynthia Utrom (Maya Rudolph), the agents are to de-mutate his creation and bring it to her for her own experiments.

The agents find Baxter in his home after he has perfected his mutagen serum, and he is speaking to his first creation, a mutated fly. The men burst in, and the fly proceeds to wipe out the agents. One of them ignites a chemical canister, causing an explosion that kills Baxter. Unbeknownst to the surviving agents and Utrom, Baxter’s mutagen has fallen into the sewers.

15 years later, the Teenage Mutant Ninja Turtles – Leonardo (Nicholas Cantu), Donatello (Micah Abbey), Michelangelo (Shamon Brown Jr), and Raphael (Brady Noon) – are scouring the rooftops as they go on a mission…to get groceries without being seen. They use their ninja skills to get in and out undetected, but they decide to stop in the park for an outdoor screening of “Ferris Bueller’s Day Off”. While the brothers have fun, they long to be part of the world beyond their sewers and with the people of New York.

The boys return to the sewers trying to sneak in, but they are found by Master Splinter (Jackie Chan) coming in later than they said they would. Leo lets it slip that they wanted to see a movie, so Splinter begins to remind them why they don’t go to the outside world. He starts with his backstory of how he was an ordinary rat that got no respect anywhere, especially from humans. He found the turtles in the sewers after they touched the mutagen, and he also ended up becoming mutated into a humanoid creature. He saw that the boys were fascinated with the city, so Splinter attempted to bring them outside until humans began reacting in horror and disgust toward them, forcing Splinter to run back to the sewers and keep his sons safe. He learned ninjitsu skills and passed it down to the boys so they would learn to be safe. However, the Turtles wish to go to high school and make friends their age.

Out on the streets, a group of criminals working for the mysterious Superfly (Ice Cube) steal a vat of mutagen from a TCRI truck. After a chase with police, Superfly appears and grabs the truck out of there. He then appears to kill the criminals before taking the mutagen.

While out on the rooftops messing around with their weapons, the boys spot a girl on her scooter, April O’Neil (Ayo Edebiri), and Leo instantly gets a crush on her. She yells at them for almost hitting her with a ninja star until they see that her scooter is getting stolen. Despite his brothers’ protests, Leo chases after the criminal.

The Turtles are led to a warehouse where a whole gang of goons keep stolen goods. The gang attempts to kill the Turtles, but they put their combat skills to use and proceed to beat them all up. April shows up to get her scooter, and while the Turtles try to hide, she sees them and finds out they are mutants. Even though she is creeped out at first, she treats them to pizza and interviews them about their origins. She then shows them her investigations into Superfly and his criminal activities, but nobody has been able to find him. April gives the boys her number to contact her if they want to help her catch Superfly and break the story on him.

After some time, the boys contact April, and she sneaks them into her high school. She wants to break a big news story because she is getting over an embarrassing incident where she vomited profusely during the morning announcements due to nerves. The Turtles hope that stopping Superfly will make them be seen as heroes in the public eye, so they go around trying to find leads into Superfly’s crimes.

The Turtles get leads on major crime groups in the city to try and get closer to Superfly. They wipe the floor with multiple goons until they learn that Superfly is making a deal under the Brooklyn Bridge that night. The Turtles infiltrate the meeting while April listens in on them nearby, and they are shocked to discover that Superfly is a mutant like them, and when he sees them, he is pleasantly surprised and welcomes the Turtles. He introduces them to his group of mutants – Bebop (Seth Rogen) and Rocksteady (John Cena), Wingnut (Natasia Demetriou), Leatherhead (Rose Byrne), Ray Fillet (Post Malone), Genghis Frog (Hannibal Burress), Mondo Gecko (Paul Rudd), and Scumbug. Superfly invites the Turtles to hang with them.

The mutants go to a bowling alley, where Mikey bonds with Mondo over their equally relaxed demeanors, while Raph hangs with Bebop and Rocksteady over seeing who’s tougher and stronger. Superfly talks to the Turtles about how he considered Baxter his father and the other mutants his siblings since he took care of them. They had their own bad experience trying to go into the city and being shunned by humans. Superfly then relays his plan to the Turtles, which is to use the stolen mutagen (which the Turtles call “ooze”) to create a super weapon that will mutate every creature on Earth to make mutants the dominant species, while humans will become enslaved or killed. The Turtles are understandably uncomfortable with the plan, and April has to get them to try and not help Superfly with his goal. They are forced to go along with the plan when Superfly implies he will kill them if they refuse to join.

Superfly makes Leatherhead, Wingnut, and Rocksteady drive with the Turtles to their destination. The boys come up with a plan and use Donnie’s bo staff to hit the gas hard enough to send the other mutants flying through the windshield so the Turtles can steal their van. The mutants follow them and April, with Superfly busting in and pummeling the Turtles before getting the mutagen. While the boys try to stop him, they fail and are apprehended by TCRI goons, while April runs to get help from Splinter.

The boys are captured by Utrom, who proceeds to “milk” them for their DNA in an attempt to create her own super mutants. Mikey and Raph get weakened until Splinter arrives and proceeds to kick TCRI butt and knock out Utrom’s goons. Before they leave, Splinter takes the time to admonish his sons for disobeying him and nearly getting killed, saying that they must listen to him and never leave the sewers if they want to survive.

The heroes find Superfly’s lair as he begins to activate his weapon. The Turtles manage to get through to the other mutants, who all admit they don’t want to destroy humanity for their own gain. Superfly gets pissed and decides to turn the weapon on himself, so the Turtles and mutants join forces to fight Superfly. When they manage to gang up on him, he tries to call out to Splinter, knowing he hates humans too and sees this as the only way the mutants can live in peace. Splinter realizes he doesn’t want to be like Superfly and helps the others push him against the machine, knocking it down and sending it into the river.

Unfortunately, the ooze seeps into the water, and Superfly fuses with underwater creatures to turn into a kaiju called SuperDuperFly. He makes his way into the city and fuses with zoo animals to get bigger and stronger before he proceeds to terrorize the city. The Turtles and mutants resolve to go out there and fight him after Splinter tells the boys he was wrong about his views on the outside world.

When the Turtles arrive in the city, the news reports claim that they are part of a mutant gang that is attacking Manhattan, which disheartens them since they think they will always be seen as monsters. Leo then tells his brothers they should not be heroes just to be accepted, but because it’s the right thing to do. He then tells them to use their strengths (Mikey with improvising, Donnie with ideas, and Raph with getting big and loud) to find a way to defeat Superfly. Donnie says to get a TCRI serum that will de-mutate Superfly by throwing it into his blowhole. Meanwhile, April goes to a news station as it is under attack and takes the time to tell all of New York that the Turtles and mutants are good guys fighting a real villain.

The Turtles make their attempt to de-mutate Superfly, but he grabs them with his claw and begins to try and crush them. Splinter tries to deliver the serum but gets knocked away several blocks. He is then surprised when a human man offers to help, and soon, other New Yorkers work together with the mutants to deliver the serum back to the Turtles. While Superfly is pelted with garbage, the Turtles seize an opportunity to throw the serum into his body, causing all the animals he fused with to return home while he becomes a regular housefly again. The people of New York then cheer the Turtles on as heroes.

Splinter allows the other mutants to come live with him and the boys in the sewers, while he and Scumbug start a relationship (to the Turtles’ disgust). The boys then enroll in high school, where they are all immediately accepted, and April is now viewed among her peers as a hero along with the Turtles.

Midway through the credits, the Turtles’ lives in high school are shown. Donnie starts a computer club, Raph joins the wrestling team, Mikey joins an improv class, and Leo helps April investigate into TCRI, who have disappeared after the Superfly incident. April later joins the Turtles at prom, all unaware that Utrom is monitoring them and making plans to recapture them, while keeping the de-mutated Superfly in a jar. She then orders help from a mysterious assassin…The Shredder.

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The Teenage Mutant Ninja Turtles - Leo, Donnie, Mikey, and Raph - wish to be part of the surface world with humans in New York City, but Master Splinter forbids them due to his hatred and distrust of humans. The boys meet April O’Neil, an aspiring reporter, and they help her track the mutant criminal known as Superfly.

Superfly was created by mad scientist Baxter Stockman, along with other mutated creatures. Cynthia Utrom, head of TCRI, wanted Baxter’s mutagen to create her own super mutants, while Superfly wants to eliminate humans and mutate every creature on Earth to make them the dominant species. After failing to stop Superfly, the Turtles are captured by TCRI to be drained of their blood until April and Splinter show up to save them.

The Turtles convince the other mutants to turn on Superfly, and they manage to destroy his weapon, only for him to be covered in mutagen to fuse with other animals and turn into a kaiju. After April convinces the people of New York that the Turtles and mutants are good guys, the humans help the Turtles deliver a serum that de-mutates Superfly.

The Turtles are seen as heroes and enroll in high school while Splinter lets the other mutants live in the sewers with them. Meanwhile, Utrom is still making plans to recapture the Turtles and is bringing in none other than The Shredder to go after them.