Children of Time tells two separate stories in alternating chapters. The first chapter tells the so-called "human story" and the next tells the so-called "spider story."
Set on a ship called The Brin 2, the first chapter of Children of Time introduces readers to Avarna Kern, who is one of the main characters in the novel. At the start of the novel, Kern is looking out a window in her ship at a green planet, which she secretly calls "Kern's Planet." It is Kern and her ship's mission to explore and terraform the green planet so that humans will have a place to live outside of Earth. Though there are other people on similar missions on different planets, Kern feels that her mission is exceptionally important because of an added component: she must release monkeys and a complex nano virus to see if the lifeforms on the green planet can evolve just like humans did. The goal of this experiment is to create a lower class which will become slaves to humanity. Some care more about creating the subservient class; Kern cares more about the experiment itself.
But before Kern's experiment is able to go forward, trouble ensues. As she goes to send the monkeys and pod containing the virus to the planet's surface, a man in the engine room who was meant to accompany the pod to surface tells Kern that he was put on the mission to prevent Kern's mission from moving forward. He, and a group he is a part of (called the NUNs), believes that humans should be the only species in the universe.
The man's goal is to not allow Kern's experiment to come to fruition. He messes with the pod and with the container carrying the monkeys. He also tries to make the ship inoperable. Once Kern learns of the man's efforts to sabotage her ship and experiment, she rushes to first save her crew. But when she is unsuccessful in doing that, she works quickly to ensure the viability of her experiment. She releases her experiment, but the monkeys die as a result of the man's meddling. Kern uploads a portion of her brain into the pod and creates a distress signal which she knows will not be answered by Earth for over 40 years. Kern is then put into cryo sleep by the pod's artificial intelligence.
Fourteen years later, Kern is awakened by the pod's AI, who tells her that a mysterious signal has destroyed every signal in the universe, including every signal from Earth. Kern survived because she uploaded her brain to the pod. But Kern is trapped in the pod for an inordinate amount of time, dismayed that her experiment has seemingly failed. Her experiment, though, did not fail. The virus survived the fall to the planet and has infected a spider which has laid an egg of a new species that will take over the planet.
The novel then flashes forward to 2,000 years in the future. The novel's focus then shifts to a man named Holsten Mason, a classicist. The engineer and the commander of the ship he is on tell Mason that they have intercepted an unknown signal. Mason quickly recognizes it as a distress signal from the "old Empire" near a planet which old star maps had said was habitable. Almost every crew member goes into cryo sleep as the ship goes to the planet.
Two years later, the crew wakes up and Mason is informed that the planet was an old terraforming project of the "old Empire" that was meant to be their home. Eventually, Mason deciphers the distress call and determines that there is life living on the planet and after a small mutiny, they take a shuttle down to the surface of the planet to investigate.
A number of generations later, the "spider story" begins with a new Portia (the first spider to lay an egg infected with the human virus) and their relatives embarking on a war against colonies of ants who are not especially smart. In the meantime, the ants set fire to one of the spiders' cities, much to their chagrin. Subsequently, Portia and her relatives return to their homebase, called the Great Nest, where they will meet and try to figure out a peaceful way to end the war.
Portia and her female friends decide to plant an explosive device in an ant colony with the help of the scent of beetle which lives among the ants. But the device goes off before it was supposed to. Regardless, the ants where overwhelmed by the chemicals in the explosive device, allowing Portia to make the ants follow her orders.
Meanwhile, Mason wakes up on the surface of the planet after his expedition party crashed landed on the surface. Mason sends someone out of their shuttle to check the air to make sure it is breathable. However, they are attacked by a group of ants. Many of the humans die and are subsequently examined by the spiders, who believe that their arrival is a gift from God. Mason, however, survives another day.
Many years later, a plague sweeps through the spider society, and they are unable to find a cure for it. Eventually, they discover the existence of the nano virus. They use this knowledge to create a serum that insulates the colony against the virus, but many spiders are killed, which leads to something called the Understanding between the spiders.
Eventually, as humans continue to return to Kern's planet, the spiders grow angrier and angrier. And then, they attack humans for their creation of the nano virus and their encroachment on the planet (Kern advises them to eradicate humanity). Rather than following Kern's advice to kill all of humanity, though, the spiders redevelop the nano virus so that it will attack humanity. It rewires human's brains to not see the spiders as a threat; instead, it rewires human's brains to see the spiders as their children. Finally, driven by their curiosity and desire to learn more about the cosmos, the spiders set out an exploration mission of their own with Portia leading the crew.