Edward Norton injured his back during filming, breaking three vertebrae after his horse threw him onto some rocks. He has said in interviews that he did not seek proper medical treatment until he had finished filming and had returned to Hong Kong.

Edward Norton personally recruited Naomi Watts for her role in the film.

Warner Independents and Yari Groups brought in a Chinese production company to help finance the film. The Chinese partner was granted approvals over the script and the finished film. It was concerned about the film's depiction of the uprising during the Chinese Revolution as well as the cholera's victims and asks for these contents to be reduced, something Edward Norton and John Curran disagreed upon. In the end, about 38 seconds of footage were removed.

Liev Schreiber said in an interview that Naomi Watts "forced them to hire me" for The Painted Veil. "She wanted to continue our relationship, and the only way to do that was to take me on the road with her."

Nicole Kidman was considered for the leading role.

Greta Garbo starred in a version of "The Painted Veil" in 1934.

Sally Hawkins had filmed a part, but her scenes were cut from the final film.

Naomi Watts and John Curran previously worked together when he directed her in We Don't Live Here Anymore (2004).

German Film Award-winning director Caroline Link was attached to the project, also working on her own version of the screenplay.

The film was originally being developed by Yari's Stratus Film. When Stratus executive, Mark Gill, left for Warner Independent, he brought this project with him.