British Museum curator Lady Alex Lindo-Parker jets off to the Amazon in search of Victorian explorer Percy Fawcett's lost camp. A series of mishaps sees her joined by maverick American adventurer Hooten and they stumble upon El Dorado.

Hooten asks Lady Alex to help him search for the Sibylline Books - a collection of lost mystical prophecies from ancient Rome. The British Museum curator accepts, but quickly finds herself scaling the Sistine Chapel, battling a sewer alligator and clashing with the Mafia.