Robert Downey Jr. was set to play Zeke Jackson (a "former Union army gunslinger"), but dropped out due to scheduling conflicts. Within the month, the character was then re-named Jake Lonergan, re-written to be an outlaw, and Downey, Jr. was replaced with Daniel Craig.
Harrison Ford wanted to go bareheaded in the film and not wear a hat (he is most famous for his performance in Steven Spielberg's Indiana Jones films, where Jones wore a fedora), but since it was a Western film he was convinced to wear a hat. In American Graffiti (1973), Harrison Ford was asked to cut his hair (to go bareheaded with a period haircut) for the film. He refused, stating that his role was too short, and offered to wear a hat instead.
As with most films distributed by Universal Pictures, there is a brief promo after the end credits for Universal Studios. However, the promo used at the end of this movie uses the decidedly 1960s era ad to promote the Universal Studios back lot tour in Hollywood, California. This promo was replaced in 1990 when Universal Studios opened a second location in Orlando, Florida and changed its logo.
Cowboys and Aliens director Jon Favreau starred in The Big Empty in 2003. In one of the last lines of the film, Kelsey Grammer dismisses Favreau's account of the events that had occurred as a tale "of Cowboys and Aliens."
With this film Harrison Ford has shared the screen with the first and latest actors who have played the James Bond role: Daniel Craig in this film and Sean Connery in Indiana Jones and the Last Crusade.