In 1987, Hank Pym and his wife Janet Van Dyne depart on a secret mission for SHIELD, leaving their young daughter Hope in the care of their housekeeper. As Ant-Man and the Wasp, they shrink themselves to stop a Soviet nuclear missile from hitting American soil. Janet went subatomic to drop the missile into the ocean, but it left her lost in the Quantum Realm, and she was presumed dead. In the present day, Hank tells Hope that after Scott Lang, as the new Ant-Man, went sub-atomic and managed to return to normal size, he believes that there might be a way to bring Janet back.
In the present day, Scott has been under house arrest after violating the Sokovia Accords by working with Captain America in Leipzig, Germany. He is spending his day with his daughter Cassie, who is visiting him for the day. Scott has a whole area set up with the help of Luis in his house for them to play in, including a slide that goes out the door. Unfortunately, Scott's foot breaks through the perimeter, and the FBI pays him a visit. Agent Jimmy Woo leads the inspection to make sure Scott isn't doing anything suspicious. Scott explains that he's had to get creative to entertain Cassie, including doing sleight of hand magic, which impresses Woo. The FBI leaves, and Cassie goes home with her mother, Scott's ex-wife Maggie and her new partner Paxton (both now on friendly terms with Scott after his previous adventure as Ant-Man).
With only three days left under house arrest, Scott does what he can to keep himself occupied. He takes a bath and then has a dream where he finds himself as Janet playing Hide and Seek with a young Hope. Scott later gives Hank a call, despite both him and Hope not having spoken to Scott since his arrest, telling Hank about the dream he saw. Hours later, Scott is tranquilized by something flying in the room.
Scott wakes up to find Hope driving him somewhere in a shrunken van. She lets him know that she took off his ankle bracelet and put it on a giant ant. They arrive at her and Hank's lab where they show Scott that they have created a tunnel to the Quantum Realm in the hopes of bringing Janet back. After Scott describes his dream in full detail, Hank and Hope deduce that he and Janet are connected because of the time he spent in the Quantum Realm. They are missing a key component to get the tunnel to work, so they head to meet with someone who possesses it. Hank shrinks the lab and takes it with him. They don't realize they are being watched by a transparent figure.
The three arrive at a restaurant where Hope meets with Sonny Burch, a black market tech dealer, while Scott and Hank monitor the situation from outside in the van. He knows Hope as "Susan", but he has already figured out her identity by the time she arrives. Burch refuses to give up the component that Hope needs unless she and Hank allow him to exploit the Quantum Realm for financial gain; Hope refuses and appears to leave. Burch and his goons start to walk out, but they are knocked around by Hope in her Wasp suit. Scott is impressed to see that she has wings and blasters. She fights them in the restaurant's kitchen and manages to grow a salt shaker to knock out one goon while also running across knives being thrown at her. As Hope grabs the component, she is attacked by the figure from earlier, Ghost. She is able to phase through anything, which means Hope's punches go through her. Scott joins Hope as Ant-Man in a new suit to help her, but Ghost escapes and makes her way to the van and steals the lab from Hank.
Scott brings Hope and Hank to hide at X-Con, the security company run by Luis, with Dave and Kurt as his employees. There, they try to come up with a plan to get the lab back. Hank figures that he has to reluctantly seek help from a former friend and partner of his, Bill Foster, a former colleague of Hank's at SHIELD, now a professor of quantum physics at the University of San Francisco.
Ghost, whose real name is Ava, goes to her home. She phases involuntarily and must sleep inside a special chamber to control the phasing.
Scott, Hope, and Hank go in disguise to the university that Bill teaches at. He maintains a grudge with Hank over the work they did together decades earlier, Project Goliath, in which Bill reached 21 feet. Scott then sees Woo and his fellow agents outside, thinking they know he's in there. Before they go, Bill tells them that they can locate the lab by modifying a defractor on one of the suit's regulators. Hank says they can't use the new Ant-Man suit because it's a work-in-progress, so Scott tells them they can find it in the older suit, which is in a trophy that Cassie took to school for show-and-tell.
Scott and Hope sneak into Cassie's school, but the regulator on Scott's suit malfunctions, making him the size of a child. They get to Cassie's classroom and get the suit out of the trophy before they are spotted.
The trio locate Ava's home and find the lab, but she knocks all three of them out and has them tied up. She reveals she is working with Bill, who took her in as a child. Her father, Elihas Starr, a former colleague of Hank's who was discredited and fired by Hank for trying to steal his research, had attempted an experiment to reach the Quantum Realm in a desperate attempt to restore his credibility, but his own tunnel became unstable. Elihas ordered his wife and daughter to escape, but the little girl ran back for her father. The tunnel caused a huge explosion, killing Elihas and his wife but Ava survived and her molecules became destabilized, resulting in her phasing. Bill tried to take care of her, but SHIELD saw an opportunity in her condition and weaponised her as a spy and assassin. The suit she wears and the chamber she sleeps in mitigate the pain caused by Ava's condition, but the condition is progressive, and Ava is living on borrowed time before she fades out of existence completely. She and Bill now plan to use Janet's quantum energy to help turn Ava normal, even if it might kill Janet. Hank fakes having a heart attack to get Bill to grab a tin of Altoids for his meds, which really contain Hank's trained ants that grow to a large size and help free them, allowing the three to escape and take the lab back. A furious Ava, warned that she has only two weeks before her condition progresses to terminal, suggests taking Cassie hostage as leverage against Scott, but Bill threatens to abandon her if she resorts to such tactics.
After regrowing the lab, Scott becomes connected to Janet, who proves herself to Hope and Hank as she helps stabilize the tunnel and enter the coordinates to locate her, but she warns them that they only have two hours before the Quantum Realm becomes so unstable they won't be able to reach her for another century.
Burch and his goons go to X-Con and interrogate Luis, Dave, and Kurt using a truth serum (though the villains insist that's not what it is). Luis reveals that Scott is with Hope and Hank in the woods where they set up the lab. Ava appears after having heard this information, and she takes out the wheels on Burch's van as she heads to find the heroes herself. Burch then contacts the crooked FBI Agent Stoltz and tells him where Scott will be. Stoltz tells Woo, and Luis quickly warns Scott so that he can return home before he is caught escaping his house arrest. Cassie is with him and says he could use a partner to help him, meaning herself, but Scott says he has Hope, which Cassie thinks is also a good fit.
Hope and Hank are caught by FBI agents once they shrink the lab. Stoltz grabs it but he is killed by Ava before he can take it to Burch, who then takes the lab herself. Scott uses the trained ants to help Hope and Hank break out of the FBI headquarters. The ants guide the three to the lab's location, and Luis joins them as backup. Hank uses the giant ants to get Bill out so that he can use his old suit to go into the Quantum Realm and find Janet, though Hank promises to help find a cure for Ava once Janet is found. The lab is shrunken again, and Luis grabs it. Scott, as Ant-Man, is attacked by Ava, but he holds her off long enough for Hope and Luis to get away.
Scott flies away on a flying ant to meet up with Hope and Luis at the rendezvous point, but they are followed by Burch and his men, as well as Ava. Hope shrinks and grows the van to literally throw the goons off, even growing a Hello Kitty Pez dispenser to throw at one of them. Scott grows to Giant Man to stop them, but as Ava intervenes, Hope becomes The Wasp to fight her. Burch takes the lab and runs to the docks where he boards a ship to get away. Scott grows again to reach him and stop him to recover the lab. Luis shows up in another car to meet with them, but Scott gets light-headed from being so huge that he falls into the water. Hope swims down to save him.
In the Quantum Realm, Hank nearly loses his signal, but he finally manages to locate Janet at her coordinates, and they reunite with a kiss. Meanwhile, the lab has grown to its normal size, and Ava and Bill are planning to get Janet's quantum energy. Hank and Janet start to return as Ava and Bill begin the process, which starts to drain Janet. Scott and Hope show up and disable their machine, giving Hank and Janet enough time to come out of the Quantum Realm. Hope reunites with her mother at last. Janet then sees Ava's problem, and she puts her hands on Ava, transferring quantum energy to Ava to stabilize her and stop her phasing. Everyone leaves as the heroes take the lab. Ava begs Bill to leave her behind, traumatised by what she's done as Ghost, but he refuses to abandon her. Outside the lab, Dave and Kurt help Luis incapacitate Burch and his goons before injecting them with truth serum as the cops arrive, leading to their arrest.
Woo thinks he knows Scott is out on the streets as Ant-Man, but he goes to his home and finds Scott there. Scott's sentence is finally over, and he is a free man once more. The first thing he does is go see Cassie.
In the final scene, Luis gets a new client for his business to keep them from going under. Hank brings Janet to the beach where they set up a new house that he grows. Scott shrinks himself, Hope, and Cassie in a car so they can use a laptop as a screen like a drive-in movie. They are then bothered by a large butterfly.
During the post-credits scene, Hank and Janet have set up the Quantum Tunnel in a van on a rooftop with Hope's help so that Scott can enter it. He obtains quantum energy to keep helping Ava be stabilized. Just as Scott is ready to go back, the others fail to bring him back, and he doesn't hear anyone on the other end of the radio. Back in the real world, Hank, Janet, and Hope have all been turned to ash by Thanos snapping his fingers (at the end of Avengers: Infinity War), leaving Scott forever trapped in the Quantum Realm with no chance of getting back to Earth. Most of San Francisco appears to have felt the effects of the Gauntlet; more than half of all life in the city and on Earth and the entire universe is gone... excluding the giant ant, who is still in Scott's apartment playing on his drum-set.
Ant Man and the Wasp will return...?
