The film begins with Edward Van Sloan stepping from behind a curtain and delivering a brief caution before the opening credits:
How do you do? Mr. Carl Laemmle feels it would be a little unkind to present this picture without just a friendly word of warning: We are about to unfold the story of Frankenstein, a man of science who sought to create a man after his own image without reckoning upon God. It is one of the strangest tales ever told. It deals with the two great mysteries of creation; life and death. I think it will thrill you. It may shock you. It might even horrify you. So, if any of you feel that you do not care to subject your nerves to such a strain, now's your chance to uh, well, ––we warned you!!
Immediately following his success in Dracula, Bela Lugosi had hoped to play Dr. Frankenstein in Universal's original film concept, but the actor was expected by Carl Laemmle, Jr. to be the Monster (a common move for a contract player in a film studio at the time) to keep his famous name on the bill. After several disastrous make-up tests (said to resemble that of Paul Wegener in The Golem), the Dracula star left the project. Although this is often regarded as one of the worst decisions of Lugosi's career, in actuality, the part that Lugosi was offered was not the same character that Karloff eventually played. The character in the Florey script was simply a killing machine without a touch of human interest or pathos, reportedly causing Lugosi to complain, "I was a star in my country and I will not be a scarecrow over here!" Florey later wrote that "the Hungarian actor didn't show himself very enthusiastic for the role and didn't want to play it." However, the decision may not have been Lugosi's in any case, since recent evidence suggests that he was kicked off the project, along with director Robert Florey when the newly arrived James Whale asked for the property. Whale had been imported from England by the Laemmles and given a free hand as to his choice of projects at Universal. He was immediately attracted to Frankenstein and greatly revised the script and conceptualization of the project, which had troubled the management. Florey and Lugosi were given the Murders in the Rue Morgue film, as a consolation. Lugosi would later go on to play the monster in Frankenstein Meets the Wolf Man a decade later, when his career was in decline (in the original shooting script the Monster spoke, cancelling Lugosi's initial objection to the part).
Actors who worked on the project were, or became familiar to, fans of the Universal horror films. These included Frederick Kerr as the old Baron Frankenstein, Henry's father; Lionel Belmore as Herr Vogel, the Bürgermeister; Marilyn Harris as Little Maria, the girl the monster accidentally kills; Dwight Frye as Frankenstein's hunchbacked assistant, Fritz; and Michael Mark as Ludwig, Maria's father. Although Kerr died a year and a half later, Belmore and Mark appeared in other Universal films and Frankenstein sequels, such as Son of Frankenstein.
Jack Pierce was the makeup artist who largely designed the iconic "flat head" look for Karloff's monster, although Whale's contribution in the form of sketches remains controversial; the question of who actually contributed what to the makeup design will likely never have a satisfactory answer.
Kenneth Strickfaden designed the electrical effects used in the "creation scene." So successful were they that such effects came to be considered an essential part of every subsequent Universal film involving the Frankenstein Monster. Accordingly, the equipment used to produce them has come to be referred to in fan circles as "Strickfadens." It appears that Strickfaden managed to secure the use of at least one Tesla Coil built by the inventor Nikola Tesla himself. According to this same source, Strickfaden also doubled for Karloff during the creation scene, as Karloff was afraid of being burned by sparks being thrown off the arcing electrical equipment simulating lightning. Although he was partially covered by a surgical drape, Karloff's abdomen was otherwise exposed during the scene and the high-voltage arc "scissors" threw white-hot bits of metal when they were used to create flashes.
There is no musical soundtrack in the film, except for the opening and closing credits.
The film opened in New York City at the Mayfair Theatre on December 4, 1931, and grossed $53,000 in one week.