Dev Anand was approached by director Tad Danielewski and writer Pearl S Buck about making a film set in India for Hollywood. After Narayan's novel was selected plans began forming to film an English and Hindi version together. Filming a shot in one language immediately followed by the same shot in the other would save time and money. But differences between the two directors made this impossible. The English version was completed first, and then the Hindi version was shot with a new script and directed by Dev Anand's younger brother Vijay Anand. Dev Anand writes in his autobiography. "Not a single shot taken in the English version would be repeated or included in its Hindi counterpart. The story outline was to be the same but the treatment completely different. It meant doing the same film twice, for two diametrically opposite tastes, the eastern and the western." While Guide (1965) (India) became an award winning classic, appearing on "best of" lists, The Guide (US) flopped badly at the box office and is rarely shown.

R.K. Narayan disliked the film adaptation of his novel. Reviewing the English version of the film for the magazine 'Life', he called it "The Misguided Guide".

There is a cut of this film that is near six hours long that was shown at Drexel University.

Compared to Guide (1965) (India), this version of the story introduces new characters and expands the role of the TV reporter. It also includes a sequence in the US Embassy in Delhi. This version includes brief nudity (body double) and a scene that implies Dev Anand's character has had sex with the heroine.

Vyjayanthimala and Leela Naidu were considered for the heroine role, before Waheeda Rehman won the role.