Spin details Earth's response to an artificial membrane placed around the planet which selectively blocks and filters incoming electromagnetic radiation, blocking out the view of anything beyond minimal low Earth orbit. The novel is told in first person, from the viewpoint of Tyler Dupree. Tyler is a close childhood friend of Jason and Diane Lawton, twins of E. D. Lawton (a wealthy industrialist who makes his money from the developing aerostat business). As children, Jason, Diane, and Tyler witness the dramatic arrival of the "Spin", as the phenomenon comes to be known, when the stars suddenly disappear one night as they are looking at the sky. Initial experiments show that the membrane is permeable, allowing space probes to pass through, but that time outside passes at a highly accelerated rate, 3.17 years per Earth second, or roughly 100 million years per Earth year. Thus within a generation, the surrounding solar system will age 4 billion years, and Earth will be destroyed by the expanding Sun.
The novel follows four primary protagonists, each of whom respond to the Spin, and to the certain knowledge that humanity is doomed, in distinct ways. E.D. founds a low Earth orbit satellite company (using high-altitude balloon technology) and profits spectacularly. Jason becomes a scientist and devotes himself to trying to understand the "Spin" and what or who is behind it. Diane joins a religious cult who views the Spin as part of God's plan for the end times. Tyler becomes a medical doctor who immerses himself in his work, but suffers through a series of existential crises related to the Spin and its obviously alien purposes.
When two huge technological constructs are detected floating above the poles right outside the Spin membrane, a physically impossible feat since, as far as we know, anything above Earth's orbit simply drops once it stops (geostationary devices only stay so by moving fast enough and near the equator), it becomes clear that the Spin has a "who" behind it, not a "what". Humanity starts calling its hypothetical authors, kind of appropriately, "the Hypotheticals", and attempts start at discovering who they are, why they're doing this to Earth, and how could humans stop them before it's too late.
The first attempt is to destroy one of the pole-floating devices with a thermonuclear explosion. The attempt shatters the membrane, causing it to becomes temporarily partially transparent, and then humans in general are able to see the astounding speed at which stars are "spinning" in the sky. But other than this, nothing really happens: the floating device attacked keeps intact, the membrane recovers in a matter of a few hours (Earth time), and things just go back to the way they were right before the explosion.
The second attempt to stave off extinction happens when the world powers decide to terraform Mars, something possible thanks to the vast rate at which time progresses outside Earth. Human colonists are sent to Mars to start a new civilization and, over the millennia (weeks on Earth), to develop science way ahead Earth's, to seek answers as to why the Spin exists and, if possible, to find a solutions for it and save Earth. After 100,000 years, roughly at the same moment Mars is engulfed by its own Spin membrane, the Martian government sends the scholar Wun Ngo Wen to Earth. Wun provides Earth the technology to send Von Neumann machines that will self replicate throughout the galaxy in search for information about the Spins creators and broadcast it back to Earth and Mars. However, within a few years of Earth time, the signals become weaker, contradictory or corrupted.
Wun also brings a collection of advanced medical technology, including a drug that brings about an upgrade in human beings known as the "Fourth Age." This is used to cure Jason's "atypical multiple sclerosis" (AMS) and Diane's "cardiovascular wasting syndrome" (CVWS).
The final explanation behind the Spin is that it was created by self-replicating machines similar to those humans sent out, but far more advanced, billions years old self-conscious galaxy-spanning collective entity. The earlier corruption of the Earthly information-seeking machines, it's discovered, was caused by them being both (materially) consumed by the more ancient network of self-replicating machines, as well as (technologically) assimilated by it. Before it's fully absorbed by the Spin-creator network, the human-created network returns evidence that other planets outside the Solar system have been contained by similar Spins, but ultimately it is the technological assimilation of one network by the other that allows humans to indirectly detect the Spin-creator network and infer its objectives, at least as far as humanity is concerned.
What is inferred is that the Spin-creator network put planets with sentient species into a state of almost suspended animation as soon as it detects they've entered a phase of unsustainable growth that will destroy them and their home planet due to resource starvation. While these planets are suspended, the machines construct huge wormhole-based gates connecting planets of similar conditions to those that were suspended, in a long chain of interconnected planets of similar environment and habitability. This is supposed to compensate for the inefficiencies of space travel as a mean of propagation, saving those sentient species from their own self-destruction by providing them greatly expanded means of development.
At (approximately) 4 Billion AD, a few years after "the Hypotheticals" have shutdown the time-warping properties of the Spin membrane (although not the membrane itself, since the Sun, having already noticeably expanded by then, would kill life on Earth were the Spin completely displaced), the Earth governments, fearing the disrupting effect of Martian biotechnology, starts to hunt down humans who have gone through the Fourth Age treatment. Jason is long dead, but Diane, being a Fourth, must hide. Tyler, who is with her, also undergoes the process of becoming a Fourth, and by the end of the book both run away from the governmental persecution by leaving Earth, going through the wormhole gate to the next Earth-like world in the sequence.
It should be noted that the first half of the story is told in the form of notes and memories written by Tyler during his Fourth treatment, which encompasses the "in the present" chapters of the first half of the book, as well as a substantial part of the second half.