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Meg Murry sits in her attic bedroom, freaking out – partly because there's a storm, but more because she feels all wrong. Her teachers think her stupid, her friends think she's a baby, and she beat up a boy for talking smack about her younger brother. It doesn't help that her father has disappeared. Meg hates herself for being unable to hold in her feelings and act normal like everyone else. She goes downstairs to make some cocoa, and finds her younger brother Charles Wallace is expecting her, and already has some cocoa going. Charles Wallace is the sibling Meg feels closest to – not only does it seem like he can read her mind sometimes, but he's also an oddball like her. Everyone thinks he's slow, but really he's smarter than most people.
Mrs. Murry joins them in the kitchen, and among the cocoa and sandwiches Meg feels much better, though still depressed that her mother is both gorgeous and brilliant while Meg thinks she hasn't inherited either of those qualities. Charles Wallace tells them about his new friend Mrs. Whatsit, and soon afterward Mrs. Whatsit herself arrives, looking like a tramp in a mismatched assortment of scarves. Mrs. Whatsit seems to know more than she should about the Murry household. After downing a sandwich and emptying out the water from her galoshes, Mrs. Whatsit leaves – but not before dropping a bomb on Mrs. Murry by mentioning something called a "tesseract."
The next morning Meg awakens thinking the strange events of the night before were all a dream, but her mother assures her that they really happened. At school that day Meg is tired and cranky. She ends up getting sent to the principal's office and giving him bad attitude, especially when he mentions her missing father. After school Charles Wallace takes Meg to see Mrs. Whatsit. Along the way they run into Calvin O'Keefe, a popular boy who's a few grades above Meg in school. Calvin and Charles click, and Calvin tells them that he had a feeling that he needed to come to this place, so he did.
The trio meet Mrs. Whatsit's friend, Mrs. Who, who is fond of quoting other people. Meg and Charles Wallace take Calvin home for dinner. Calvin tells Meg about his home life, and how he cares about his family but they don't care about him. Meg tells Calvin about her missing father, and helps him with his math homework despite being in a couple of years behind him in school. After dinner Meg and Calvin go for a walk in the moonlight, and their tender moment is interrupted by Charles Wallace telling them that it's time to go. They are soon joined by Mrs. Whatsit, Mrs. Who, and Mrs. Which.
Suddenly Meg feels that she's in nothingness, and that her body itself has disappeared. Slowly she returns to herself, and finds that she, Charles Wallace, Calvin, and the three Mrs. Ws are in a sunlit field. Mrs. Whatsit tells them that they're on a different planet, and they're going to find Mr. Murry, Meg and Charles Wallace's missing dad. Mrs. Whatsit changes into an unspeakably beautiful winged centaur and takes them on a ride to the top of a huge mountain, stopping along the way to pick up some oxygen-producing flowers so they won't suffocate from the thin atmosphere. From the top of the mountain they see a dark shadow blotting out the stars that gives them a feeling of great evil.
Mrs. Which tells them that Mr. Murry is behind the shadow, and that that's where they must go to find him. Mrs. Whatsit explains how they travel through time and space so quickly: it's a tesseract, a wrinkle in time, that takes them through the fifth dimension. The group tessers again, stopping briefly on a two-dimensional planet that doesn't work very well for the human members of the party, and arrives on a grey, foggy planet that is the home of the Happy Medium.
The Medium shows them Earth, and they see that the same Black Thing that was blotting out the stars is also wreathing their own planet. The Medium shows them the Black Thing in a different part of the universe, and they watch as a star sacrifices itself to destroy the Black Thing. They realize that Mrs. Whatsit, Mrs. Who, and Mrs. Which were all once stars, and gave up their starry lives in battle with the Black Thing. Now the Medium wants to show them something happy, so she shows them their mothers, but Mrs. O'Keefe is screaming like a banshee and Mrs. Murry is crying alone. That didn't work so well as a cheering-up strategy. It does at least make Meg mad, which drives away her fear.
They tesser again and land on the planet Camazotz, which is where Mr. Murry is, and which has succumbed to the Black Thing. Mrs. Whatsit, Mrs. Who, and Mrs. Which leave, but not before giving each of the humans a gift to help them on their way. The kids head through the suburbs into town, and notice something odd: all the children in front of the houses are bouncing balls and jumping rope in the exact same rhythm. There's one boy who's off-beat; they talk to his mother, and she seems very scared. They arrive in the city and see a newspaper delivery boy throwing newspapers with impossible accuracy. They ask him some questions, and he tells them that this is the capital city of Camazotz, which is home to CENTRAL Central Intelligence and IT. Charles Wallace thinks that's where they should go, Meg isn't so sure. Calvin agrees with Charles but also has a feeling that they're going into great danger.
They enter the giant CENTRAL Central Intelligence building and talk to a man who decides to report them for not conforming. He sends them off to a man with red eyes who speaks directly into their brains without moving his lips. He tries to take over their brains in other ways, but the children resist by reciting nursery rhymes. Charles Wallace looks into the man's eyes in an attempt to figure out who he is, and almost gets hypnotized before Meg brings him back to himself by tackling him. Meg complains to the man with red eyes that if they're going to be mind-controlled, he could at least have the decency to feed them first. The man summons a turkey dinner. It tastes fine to Meg and Calvin, but not to Charles, whose mind is stronger than either of the others: the taste of the food is a mental suggestion from the man, not from the food itself. Charles Wallace thinks that the only way to find their father is for him to mindmeld with the man and hope he can get back to himself afterwards. Charles Wallace submits to the man's control and turns into an obnoxious brat who's nothing like the real Charles Wallace. (We'll call this annoying version of Charles Wallace Chucky).
Chucky takes Meg and Calvin to their father. On the way, Meg reminds Calvin that Mrs. Whatsit said he has the gift of communication, and tells him to unwrap that gift on Chucky. Calvin tries but doesn't quite succeed. Chucky drones on about the glories of the planet of Camazotz, and how it's a perfect place because everyone is exactly the same, without the troubles caused by free will. They pass a room where they see the off-beat boy from earlier, screaming in pain as he gets shock therapy to make him bounce his ball in time with the rhythm.
They arrive at a room in which Mr. Murry is imprisoned in a kind of glass column. Meg puts on her gift from Mrs. Who – a pair of glasses – which take her through walls into the room and into the cylinder where her father is held prisoner. Meg is ecstatic to be finally back with her father, and tries to explain to him everything that's happened. She gives him Mrs. Who's spectacles so he can see, and they leave the cylinder, into the room where Chucky is waiting.
Chucky takes them all to see IT, which turns out to be a giant pulsing brain. Their very lungs and hearts are forced to follow IT's rhythm. Meg tries to resist by reciting the opening lines of the Declaration of Independence, and Chucky tells her that on Camazotz they have absolute equality because everyone is exactly alike. Meg has a moment of clarity: being like and being equal are not the same thing. Mr. Murry grabs Calvin and Meg and tessers the heck out of there.
Meg slowly regains consciousness, feeling like she's been flash frozen. She hears her father and Calvin talking, but not Charles Wallace. Her father tells Calvin that he had been on a top-secret government experiment and had tried to tesser to Mars, but ended up on Camazotz instead. He hopes to return to tell his colleagues how little they understand about the forces they were playing with. Meg revives enough to ask where Charles Wallace is. She's seriously mad that they just left him there, even though her father tries to explain that it was the only thing they could do. Meg is also disappointed that finding her father didn't just fix everything.
Some strange-looking inhabitants of the planet they landed on, furry beasts with tentacles and no eyes, arrive and carry off Meg to take care of her. Mrs. Whatsit, Mrs. Who, and Mrs. Which arrive, and tell Mr. Murry and Calvin that for various reasons they can't return to Camazotz. On the subject of Meg they are silent, and eventually Meg realizes that she's the only one who can return and save Charles Wallace. The Mrs. Ws take her back to Camazotz, each giving her a gift: Mrs. Whatsit gives Meg her love, Mrs. Who gives her a quotation, and Mrs. Which gives her the knowledge that she has something IT doesn't.
Meg returns to IT's chamber, and finds Chucky there with the giant brain. Chucky messes with her, eventually telling her that Mrs. Whatsit hates her. Meg says no she doesn't, Mrs. Whatsit loves me. At that moment Meg realizes what she's got that IT hasn't got: love. She stands there and loves Charles Wallace with all her heart, and Chucky becomes the real Charles Wallace again. Mrs. Whatsit sweeps them away, and they find themselves at home with Mr. Murry and Calvin. Mr. and Mrs. Murry have a happy reunion, and there is much group hugging.