Reached opens with Xander Carrow, now a Society Official, taking information with two other Officials, including a woman named Lei, about a new baby boy in Camas Province. They administer to him a tricolor tablet of green, blue, and red, designed to immunize him to diseases and infections throughout his life. Xander mentally notes that he has switched out the tablet with ones created by the Rising which, in addition to the regular immunizations, also immunize the consumer to the Society’s red tablets. He and the Officials are alarmed to learn that the older sibling of this baby suddenly won't wake up. They rush him to the hospital and learn that he is very sick, and that Xander, the other Officials, and the boys' parents will all need to be quarantined for their own safety.
Meanwhile, Cassia Reyes is in her apartment waiting to be able to see Ky Markham, her love and partner who currently works as a pilot for the Rising in a Camas. She is upset to learn that she has been assigned extra sorting for that evening, which will interfere with this visit. The sort proves very strange, and when someone comments that they're sorting Matches for that night's Matching Banquet, all sorters are instructed to consume their red tablets. Cassia slips a paper up her sleeve that says "Remember" and consumes hers.
Ky and Indie Holt are pilots for the Rising. They are called out to their ships for a drill that turns out not to be a drill; the Rising has, in fact, begun.
Cassia feels foggy as she takes the train home, unable to recall what happened until she finds the "Remember" paper up her sleeve. This informs her that she is not immune to the red tablet's amnesic effects the way Ky and Xander are. She gathers her thoughts by reminding herself of what she knows, including that she is a trader for the Archivists in Central, who run a large, far-reaching trading hub out of a secret location knows as the Archives. Cassia has acquired many wonderful poems which she keeps hidden in a box at the bottom of a lake in Central. She waits at this lake for Ky to come meet her, unaware that plans have changed.
Ky and Indie want to make a run to Central to see Cassia, but the voice of the long-sought-after Pilot comes over their speakers and tells them that they have a special mission to deliver cures to the Plague (as the disease is known) to their assigned Provinces. They do as they're instructed, accompanied by a runner named Caleb.
With the Rising begun, Xander is released from quarantine and taken to work as a physic--a kind of doctor's assistant--in the medical center, all the while listening to the voice of the Pilot speaking over the ports. Xander learns that Lei is not part of the Rising, but later vouches for her to be able to join it. They become close friends as they work together in the medical center.
Back at the lake, Cassia guesses that Ky is not coming and returns home to see that the ports are alive with images of the Plague victims, who are being called the "still" due to the way they lose all ability to move once infected. She realizes that the Society is falling and feels grief in spite of herself. The next day, she learns from the Head Archivist that the Plague is indeed real and that the Rising has commenced.
As the weeks progress, Xander and the other Rising medical staff seem to have the Plague under control, regularly administering the cure and sending healed patients home. Xander is in a prominent enough position that he addresses all incoming staff about their new role in the Rising and how to administer the cure to the still.
Cassia makes a trade with a woman at the Central Province Museum as part of her job as a trader. The woman wants green tablets to calm her son's worries at night. Having always been averse to the green tablets at her late grandfather's warning, Cassia instead suggests that the woman sing her son a song. She quickly writes one for her and give it to her as a gift. Later, Cassia strings up dozens of papers sporting pieces of Dylan Thomas' poem "Do Not Go Gentle into That Good Night" along the branches of a tree.
Ky receives a very delayed message from Cassia via a trader while out for a walk with Indie and the rest of their squadron. He reads it to learn that Cassia is safe from the Plague. The second half of the message is meant for Xander. Cassia hopes Ky can deliver it to him for her. When an obnoxious fellow pilot named Connor pushes Ky into the nearby river, part of the message to Xander is destroyed. Later, Ky delivers it to Xander during a cure drop-off. Xander is angry to see that the message was ruined at such a crucial place (unbeknownst to him, it was right as Cassia was going to ask Xander to let go of his love for her and find someone to be happy with). He talks with Lei about his Match and hers. Lei has begun to notice a bit of a variation on the red marks that the Plague causes in certain patients.
Cassia is approached by the daughter of the woman for whom she wrote the song, who gives her a handmade green and brown bird. Touched, Cassia talks with her about founding a place where people can create and display whatever art they want. The girl suggests the place near the marsh where the Rising is storing pieces of the white quarantine walls as they become unnecessary. This place quickly becomes a hub of artwork popularly known as "the Gallery."
Three months into the Plague, more patients are experiencing the acute rash-like symptoms than Lei previously mentioned. Xander recalls helping create black market tissue preservation samples back when he acquired blue tablets for Cassia to take with her to find Ky. After consulting a virologist, Xander realizes that the virus has mutated.
Indie and Ky are instructed to deliver a cure deposit to Oria Province, Ky's old home. They notice that Caleb has been bringing unidentified cargo back on board after each drop-off, but he refuses to say what it is when they confront him about it. Later, Indie and Ky share a kiss that neither regret but that Ky acknowledges is "nothing like [with] Cassia" (p. 187).
Cassia is witness to a trader who cheated the system being revoked of her trading privileges. The Head Archivist takes Cassia into the depths of the Archives and asks if Cassia has any tissue samples to trade, which she doesn't. Later, at the Gallery, Cassia sings and dances with a large group of people for the first time.
Xander's medical wing is receiving many new patients suffering from the mutation. They conclude that those with a red mark on their necks are immune, while those without one are at risk. They realize they must quarantine their whole wing. Lei sees that Xander has the red mark, and he discovers that she doesn't.
Weeks into the mutation's outbreak, the Provinces have descended into chaos. Caleb goes still on a mission to deliver more cures to Oria, but not before admitting that the secret cargo he's been bringing on board are tissue preservation samples that the Pilot uses to gain people's trust--he knows that there's no way to bring people back from the dead, but plays on people's ignorance of this to maintain loyalty.
Cassia is confined to her apartment in the wake of the mutation outbreak but sneaks out to the Archives, where she discovers that all the Archivists have moved to avoid the Plague. The Head Archivist arranges passage for Cassia to Camas Province at the Gallery, which is being dismantled as they use its pieces to reassemble the quarantine walls. Cassia meets Indie there and together they fly to Camas, where they meet up with Xander, Ky and the Pilot. Xander was with Lei when she herself went still. He printed out copies of the Hundred Paintings and strung them above her head for her to look at as she laid there - then Indie came to retrieve him.
The Pilot takes Cassia, Xander, and Ky on his ship. As they fly, he accuses them of conspiring against the Rising, having evidence of much suspicious activity in which they've been involved. He shows Cassia a data pod with her grandfather's microcard from his Final Banquet, and explains that Cassia's great-grandmother was once the Pilot. Cassia learns that her grandfather's favorite memory of her before his death was something called the "red garden day," which she can't recall. Tragically, she also learns that her parents have gone still. The Pilot is taking them to the stone village known as Endstone to help find a cure for the mutation before it's too late. Ky begins to show symptoms of the mutation as they fly.
They are greeted when they land by a group of Anomalies led by a woman named Leyna, who escorts them to Endstone. Along the way, Ky collapses, and before going still admits to Cassia that he kissed Indie. She is hurt but realizes it doesn't matter. They bring Ky to the infirmary, where an ancient man named Oker quickly brings him an IV nutrient bag of his own making to help keep Ky from getting worse. Cassia and Xander are interviewed separately by the village leaders. Oker asks that Xander be assigned to work in his lab. The villagers are desperate to find a cure for the mutation even though everyone in the village is immune to it because the Pilot has agreed to transport them all via ship to a place beyond the Society called the "Otherlands" if they can.
In his near comatose state, Ky is aware of someone unhooking his nutrient bag.
Cassia works as a sorter, attempting to sort many items that she has never seen before and which have no pictures. She calculates that the Rising has likely begun taking some still patients off of life support, which raises the stakes in the race for the cure; if too many people die, they might as well not have a cure at all, and their leverage in their bargain with the Pilot will be gone. Meanwhile, Xander works with Oker in his lab to find the cure. Oker was once a scientist that helped the Society create the original Plague, now repurposed for use by the Rising. He escaped from the Society ten years prior, just before his Final Banquet, making him 90 years old.
Cassia meets Anna, the former leader of the farming village in the Carving where she and Ky met Hunter. Anna accompanies her to visit Ky on one of Cassia's breaks and tells her that Matthew Markham, the biological son that Ky's adoptive parents supposedly lost, was actually brought to the stone villages at his parents' request in the hopes that he could have a better life. He has since moved on to the Otherlands. Cassia asks Anna to draw for her some of the items that she isn't familiar with in her data. She realizes that Ky's nutrient bag is out and has a medic replace it, unknowingly returning Ky from deep stillness.
Cassia has a vivid flashback to a day just before her Matching Banquet when she was approached by two strangers who wanted her help with something concerning her grandfather, but she can't remember what. Xander and Cassia begin to establish a routine in Endstone, he working with Oker and she working as a sorter. Cassia is reunited with Eli and Hunter in the infirmary one day.
In his still state, Ky experiences a kind of telepathic conversation with Indie in which she reveals that she is sick with the mutation, has stolen a Rising ship, and plans to fly until she can't anymore. He pleads with her not to go, but she refuses to stay.
Oker has an epiphany about an ingredient called camassia. He takes Xander deep into the wilderness to gather a bunch of it, and they return and make several batches of cures with it. They are suddenly called to the infirmary when a few patients begin dying seemingly out of nowhere. Cassia experiences a second flashback in which she sits with her grandfather in a greenspace and discusses the meaning of a "red-letter day," also known as a "red garden day."
The villagers decide to vote on whether to give the still patients Oker's camassia cure or several different ones, as Leyna has suggested. They vote to give them Oker's cure. Cassia returns to the infirmary to find that Hunter has knocked the medics unconscious and unhooked every patients' nutrient bag.
In the lab, Oker suddenly changes his mind about the camassia cures and, despite the vote, tells Xander to destroy all of them at once so that they can't be administered. He leaves suddenly to go find what he believes is the real missing ingredient for the cure, though he doesn't say what it is. Xander destroys the cures as instructed.
Not long after, Cassia is horrified to find Oker dead on the ground, having suffered a heart attack, but not before drawing a strange, three-sectioned shape in the mud. Leyna and the villagers, hoping to have Oker help deliver more nutrient bags to the still following Hunter's actions, find Oker's body and learn that Xander destroyed the cures. They believe that Xander did this on purpose for malicious reasons, even though he insists it was by Oker's instructions. The villagers plan to vote on both Hunter and Xander's fates.
In the prison, Hunter admits that he unhooked everyone's bags, even Ky's, to give everyone the experience that his late daughter Sarah had to suffer through. In the infirmary, Anna provides Cassia with paintings of the items in her data sort that she didn't recognize. Cassia suddenly realizes that the missing ingredient in the cure is the sego lily, a three-petaled flower that Oker drew in the ground before dying. She and Anna quickly acquire some in the woods and bring it to Xander in his cell to have him make a batch of cures.
In the infirmary, Anna distracts the medics while Cassia gives Ky the new cure. His condition begins to improve immediately, especially after a second dose, but they're out of time as Hunter and Xander's trials suddenly begin. Anna stands with Hunter and helps him receive a minimum sentence of exile (rather than something worse). He is forced to leave immediately. Cassia stands with Xander, but his fate goes undecided as the Pilot suddenly lands his ship right in the town square, causing chaos and panic. The Pilot comes to say that the Provinces are descending into madness and planning to take significant portions of still patients off of life support. Cassia and Xander show him that the cure is working on Ky and he agrees to fly all of them back to the Provinces. Cassia thinks her mother knows where to find significantly more sego lily. They fly to Camas, make a bit more of the cure, and then head to Keya to give it to Cassia's mother. Along the way, the Pilot tells them that Indie got sick, stole a Rising ship, flew until she crashed, and died. Cassia and Ky are horrified to learn about Indie's death, but Ky, somehow, already knew about it. In Keya, they're greeted by Cassia's younger brother, Bram, who takes them to their mother and informs Cassia that their father died of the mutation.
Xander and the other physics administer the cure to trial patients. Results are promising; people are waking up, healed. Xander gives Lei the cure and her eyes move to look at him. When Cassia's mother regains consciousness, she tells them that the sego lily she knew of was growing in Sonoma Province, where the Rising immediately goes to retrieve as much of it as they can. The rest of Cassia's memory of the red garden day finally comes to her: she was approached by Rising Officials who asked her to complete an illegal sort to safeguard her grandfather's tissue preservation eligibility, which was in jeopardy because they learned he once stole from Society restoration sites. Cassia did as she was told and then was given a red tablet to forget. She realizes it was during this sort that she put Ky's name in the Matching pool, unbeknownst to anyone but the Rising at the time. Later, her mother confirms that her grandfather was a member of the Rising, but that her father refused to be because he wanted a normal, safe life for his family.
Ky flies to Oria Province, knowing that his adoptive parents are currently missing, and retrieves Xander's family from their home, saving them. Later, Lei regains consciousness and Xander nearly kisses her, but can't bring himself to. He decides that he wants to go to the Otherlands, feeling that he must let go of Cassia and the Provinces. Cassia learns that Lei's real name used to be Laney, the Anomaly to whom Vick once celebrated a marriage contract. She tells this to Xander.
Cassia and Ky revisit Endstone to bring Anna back as a potential candidate to lead the Provinces. Xander and Lei stay behind and confess their love for another, eventually deciding to remain in Endstone.
The Provinces hold a vote to elect one of three candidates as their new leader: an Official representing the Society, the Pilot representing the Rising, and Anna, representing everyone else. Cassia and Ky both vote for Anna, feeling hopeful about the future.