Both Joyce Mackenzie and Jane Greer were considered for the part eventually played by Gloria Grahame, wife of uncredited co-director Nicholas Ray.
Gloria Grahame did not want to be in this movie; Howard Hughes admitted that he never saw her previous performance opposite Humphrey Bogart in the film In a Lonely Place (1950), which is today unanimously considered among her finest performances. When Grahame asked to be loaned out to make George Stevens's A Place in the Sun (1951), Hughes turned down her request and forced her to make this movie (she reportedly dryly told her then-husband and uncredited director Nicholas Ray, who she was in the process of divorcing, that she wouldn't ask for alimony if he could get her out of this movie). Grahame later stated that she intentionally over-acted out of hatred for Hughes.
Jane Russel confesses in her autobiography that, during the shooting of Macao, the director Josef Von Sternberg told eating was forbidden on the set for the crew. But that did not prevent Bob Mitchum to bring a basket of food every day for the whole technicians and actors.
Producer Howard Hughes fired director Josef von Sternberg about a third of the way through and shot the rest with Nicholas Ray. However, in the Spring 1972 edition of "Focus on Film: screenwriter Walter Newman said he and Nicholas Ray were asked by RKO production boss Jerry Wald to write and direct three scenes that "tied the story together a bit." Newman sad he did a love scene in a Chinese junk with Robert Mitchum and Jane Russell.
Robert Mitchum actually wrote several scenes for this movie when Nicholas Ray came on board to do uncredited directing so that the script would make more sense.
When Lawrence Trumble is getting himself a shave, he speaks to the Chinese salon lady in Pigeon English. She replies to him asking about baseball - either Yankees or Dodgers in perfect English, shocking him. Macao was released in 1952 and in the same year, New York Yankees defeated Brooklyn Dodgers 4-3 to take the Major League Baseball title.
Jane Russell reports that director Josef von Sternberg was nasty to the crew, and would make insulting remarks about her and Robert Mitchum to each other, such as "what are we going to do with this beautiful stupid girl". Although Sternberg threatened Mitchum that he could be put off the picture, in the end it was the director who was replaced by Nicholas Ray.