Although they had both previously appeared in Hamlet (1948) and Moulin Rouge (1952), Christopher Lee and Peter Cushing met on the set of this film for the first time. They would pass the time between shots by exchanging Looney Tunes phrases, and quickly developed a fast friendship, which lasted until Cushing's death in 1994.
Christopher Lee and Peter Cushing's friendship was sparked when Lee stormed into Cushing's dressing room, complaining that "I've got no lines!" Cushing kindly responded, "You're lucky. I've read the script."
The script called for a child actress to play Hazel Court's character, Elizabeth, as a little girl of three or four in flashback scenes. Court suggested to the producers that her daughter, Sally Walsh, who looked very much like her mother, play the part. As Court said in an interview, "She hated it - HATED being in it! I think it was all foreign to her, and she didn't understand it. She still remembers it to this day, and still doesn't like it!"
Melvyn Hayes explains in the Blu-Ray "making of" feature how producer Peter Rogers told him about the casting process of the monster. According to Rogers, a memo went out indicating Hammer was looking for "someone big" to play the monster. In the end, it boiled down to Christopher Lee and Bernard Bresslaw. Both their agents were phoned, asking them how much money they wanted. Bresslaw's minimum fee was 10 pounds a day, whereas Lee's was 8. "And so, for the sake of two pounds, Christopher Lee became an international star", according to Hayes.
The original concept for this film was a black-and-white feature with Boris Karloff as the Frankenstein monster. Universal threatened a lawsuit if Hammer copied any elements from the classic Universal version. Hammer had Jimmy Sangster completely redo the script and had Jack Asher shoot it in Eastmancolor.
Christopher Lee's monster make-up was almost literally done at the "last minute". After previous attempts to design a monster make-up using a cast of Lee's head had failed, make-up artist Philip Leakey made the final design the day before shooting began, directly onto Lee's face, using primarily cotton and other household materials. Since he didn't use any latex or molds, the make-up had to be recreated from scratch every day.
The painting on the staircase shown to Prof. Bernstein is Rembrandt van Rijn's 1632 "The Anatomy Lesson of Dr. Nicolaes Tulp". Mirroring Victor's own actions, it shows the dissection of a hanged criminal, in this case armed robber Aris Kindt.
For some exterior scenes, such as that of the little boy at the river, leaves in the foreground of some shots were painted red and yellow. This gave continuity with the shots of the autumnal foliage seen in the establishing shot of the forest after the Creature first escapes from Frankenstein's laboratory.
The idea originated with Milton Subotsky, who went on to co-found Amicus Films, Hammer's main rival during the 1960s and early 1970s. The script was revised several times to avoid repeating any elements from the Universal Frankenstein series. As part of this effort, new monster make-up had to be devised especially for this film.
According to cameraman Len Harris, stuntman Jock Easton came close to being injured several times during filming. For the scene where Peter Cushing pushes him off a balcony, the floor was padded but his head missed the place where it was supposed to land. He also doubled for Christopher Lee in the climax where the creature is set on fire, and Harris recalled that there were quite a few men onset with fire extinguishers.