The novel tells the tale of Julie de Rubine, a noble orphan, who after the death of her parents moved from France to Turin, to live with her wealthy aunt Madame Laronne.
Julie was admired for her beauty, and soon had a marriage proposal from Signor Vescolini, the only son of the Conte della Croisse.
He asks her to look after a little girl, four months old, and promises her a large house to live in, a quarterly allowance, servants and career help for their son, Enrico.
On their way to Germany they met a man called La Roque, who is left ill and dying in the inn, with only his daughter to attend him.
To increase his wealth even more the Marchese de Montferrat is rumoured to hire assassins who killed Conte della Caro, his relative, whose heir he was.
Julie raises up the children, teaching them classics, languages, music, and appreciation of nature and involves them in charitable works.
Rambling in the woods, Julie stumbles upon a tower, enters to see what is inside and hears Paoli, threatening someone with death.
He tells her that his son was killed by instigation of the Marchese de Montferrat, and he himself and his daughter were running away from his vengeance, when they met Julie on the road.
Since then his daughter has married a rich and high-born German nobleman; and he was living near his family when one day he was abducted by Paoli and two ruffians.
Enrico finds her by chance in a hunting villa, guarded by Masehero, Paoli's brother, and left to die from hunger in one of the rooms below.
The Conte informs him that he killed Paoli, and that the latter confessed all his crimes and announced that Enrico's mother was a lawful wife of the Marchese de Montferrat.
Paoli, thinking that he might benefit from it in the future, produced a real priest, so the ceremony was valid, and Enrico is a lawful heir of the Marchese.
The monk who approached Laurette is revealed to be her maternal grandfather, and she is the legitimate daughter and the rightful heiress of the Conte della Caro.
According to the literary critic and bibliophile Michael Sadleir, in his survey of the Northanger Horrid Novels "The Orphan of the Rhine is a genuine product of the influence of Mrs Radcliffe.