Ten years, fifty days and three, Clau-Clau-Clau shall given be A gift that all desire but he. To a fawning fellowship he shall stammer, cluck and trip, Dribbling always with his lip. But when he's dumb and no more here, Nineteen hundred years or near, Clau-Clau-Claudius shall speak clear.

With this prophecy from the sibyl of Cumae begins the story of Claudius, an obscure prince of the Julio-Claudian line. Ridiculed for his speech impediment, compared to a monkey and assumed to be an idiot, he ends up confounding his own expectations, and the opinions of those around him, by becoming master of the known world, ultimately revered as a god. I, Claudius tells the first 51 years of his story, from childhood up to the moment when, following the assassination of his insane nephew, Caligula, he is discovered hiding behind a curtain.

It tells the story of his relationship with his grandmother, the Empress Livia, wife of the Emperor Augustus – here portrayed as a serial poisoner who murders, among many others, her own husband and Claudius's father. Marginalised from public life, Claudius takes refuge in historical research; through the paranoid reign of Tiberius and the descent into madness of Caligula, he views events from the perspective of an observer rather than a participant. More than once, he is advised by friends to exaggerate his disabilities and to value his role as the butt of other peoples' jokes. In so doing, he develops the ascerbic wit and laconic humour that give life to his perspective on the affairs of state and the intrigues of the court.

Drawn into the orbit of Caligula's excesses, he manages to stay alive by humouring him and pandering to his delusions, whilst always retaining a clear head himself. When he finally realises that, contrary to both his political beliefs and his personal aspirations, it is his destiny to be Emperor, he consoles himself as only a historian can:

So I'm Emperor, am I?...at least I'll be able to make people read my books now...and...what opportunities I should have...for consulting the secret archives...What a miraculous fate for an historian!