Wheelers chronicles mankind's first contact with an alien intelligence, a meeting which takes place out of necessity when a rogue asteroid enters the Solar System and is set on a collision course with Earth by an advanced and hitherto unknown Jovian species as a way of avoiding a devastating impact to their own world.

The story opens with a feeling of anachronism, as two of the novel's central characters (Charles Dunsmoore, a career archaeologist and his volatile graduate student Prudence Odingo) work in the year 2194 to interpret and preserve artifacts found in the vicinity of the Great Sphinx, which is being disassembled to save it from the advancing waters of a clogged and flooding Nile River after the collapse of the Aswan Dam.

Professionally and personally embittered by the success of Dunsmoore, Prudence begins a life of semi-legal interplanetary exploration (referenced by the book but never fully explained) and makes a living selling cosmic oddities to the highest black market bidder.

This dangerous and profitable lifestyle acquaints her with legal authorities as well as the Belters—a group of Zen Buddhists (known as The Order of the Cuckoo) who have populated and mined both Earth's Moon and the asteroid belt that lies between the terrestrial planets and the Jovian worlds of the outer Solar System.

Hacking into one of the probes that Dunsmoore's been carefully bobbing around the lifeless stratosphere of Jupiter, Odingo's team sends the RCV into the lower atmosphere, immediately encountering alien lifeforms both advanced and simplistic.

A portion of Wheelers' fiction is based on hypotheses that the presence of gas giants may actually be a necessary factor in the formation of habitable terrestrial planets, as their mass deflects and breaks up potentially devastating threats.