When this film was first conceived it was supposed to have been a follow-up to King Kong (1933), but was never made. However, an early B&W version of the "cowboys in Africa" footage was shot, and wound up being used in Mighty Joe Young (1949).
This was the last film where Ray Harryhausen's stop-motion effects technique was billed as "Dynamation". Starting with his next film, The Golden Voyage of Sinbad (1973), Dynamation would be rebranded as "Dynarama".
The roping of Gwangi was achieved by having the actors hold on to ropes tied to a "Monster stick" that was in the back of a Jeep. The jeep and stick when filmed with Gwangi are on a back rear projection plate and hidden by his body and the portions of rope attached to his body are painted wires that are matched with the real ropes.
Special effects master Ray Harryhausen has said that sequence of the elephant performing its act and its subsequent fight with Gwangi were done with no shots of a real elephant because no such animal was available. However, there is an elephant in the very early scene of the Wild West show's parade through the town, and Ray's animation puppet is a perfect double for it.
Whereas all of Ray Harryhausen's past films had an "Approved" rating from the Motion Picture Association of America, the modern ratings system was introduced around this time, and this was the first film of his to get a "G" rating.
Special-effects pioneer Willis H. O'Brien began pre-production at the RKO-Pathe Studios on a story by Harold Lamb about a huge T-Rex called "Gwangi", with John Speaks as producer, in 1941. The project was canceled when studio management was changed.