Most of the action takes place on Martha's Vineyard in Massachusetts, where Lang has been holed up in the holiday home of his billionaire American publisher to turn out his memoirs on a deadline. Other scenes are set in Notting Hill, New York and Whitehall.
Lang's former aide Mike McAra has been struggling to ghost his master's memoirs but, as the novel opens, McAra drowns when he apparently falls off the Woods Hole ferry. The fictional narrator of The Ghost, whose name is never revealed, is hired to replace him. His girlfriend walks out on him over his willingness to take the job: "She felt personally betrayed by him; she used to be a party member". He soon suspects foul play and stumbles across evidence of possible motive, buried in Lang's Cambridge past. Having located what may be the lethal secret, the replacement ghostwriter begins to fear for his own safety.
Meanwhile Lang, like his real-life counterpart, has been accused by his enemies of war crimes. A leaked memorandum has revealed that he secretly approved the capture and extraordinary rendition of UK citizens to Guantanamo Bay to face interrogation and torture. One Richard Rycart, Lang's disillusioned and renegade former foreign secretary (loosely based on Robin Cook), who before and during his early days in office made much of his wish to adopt an "ethical" foreign policy, is now at the UN, in a position to do his former boss serious damage. Unlike Blair, Lang thus appears in imminent threat of indictment at the International Criminal Court.
The narrator tussles to reconcile his obligation to complete the ghosting job with its attendant abundant payment on the one hand and, on the other, the pressing need, as he sees it, to reveal Lang's true allegiances. The action really heats up when he contacts Rycart. The narrator comes under increasing jeopardy: romantically and politically, as well as physically.