When Africans Mutia Omoolu and Riano Tindama were brought to Hollywood for re-shoots, they were refused admission to the Hollywood Hotel because they were black.
According to Alfred Hitchcock, audiences at the first screening of this film laughed when C. Aubrey Smith suddenly appeared in the story.
Director W.S. Van Dyke and many of the crew contracted malaria and were treated with quinine. Two fatal mishaps occurred during the African filming: a native crewman fell into the river and was eaten by a crocodile, and a native boy was killed by a charging rhino (which was captured on film and is in the movie). Other misfortunes also plagued the production, including flash floods, sunstroke, swarming locusts, and tse-tse fly and ant attacks.
MGM secretly sent a second unit crew to Tecate, Mexico to avoid the American laws about ethical treatment of animals. Animals were shot fighting each other, and lions were reportedly starved to promote vicious attacks on hyenas, monkeys and deer.
In 2009, Harry Carey Jr. went to Africa to film a documentary called "Trader Horn: The Journey Back", a making of this movie.