This film is considered the last entry in the Golden Age of Toho's kaiju films, and meant to be the last film of the Godzilla series. However, it was successful enough that it was decided to continue the series, albeit as part of a film campaign called the Toho Champion Festival, a seasonal matinee that specifically targeted children. This meant that subsequent films would have to reduced their budgets and staff since the Godzilla films were just too expensive to continue making in their original manner. For example, this film and the ones prior had two or more large groups of crew members that divided the work on the character drama and special effects sequences. Case in point: cinematographer Taiichi Kankura shot the live action character drama directed by Ishirô Honda, while different cinematographers, Yôichi Manoda and Sokei Tomioka, shot the monster sequences directed by Sadamasa Arikawa. Subsequent films reduced this to a singular crew that had to manage all of those aspects at once.
The Japanese title of this film actually translates as "Monster Total Advancement". The title "Destroy All Monsters" was Toho's international title used for overseas sales. These titles were usually changed when the films were released in the U.S. and Europe; however, this one was kept.
The final film in the Godzilla series to involve all four "founding fathers": Tomoyuki Tanaka (producer), Ishirô Honda (director), Akira Ifukube (score) and Eiji Tsuburaya (special effects, although he only worked as an advisor).
As an apparent inside joke, the TV broadcast showing the humans under Kilaak control warns the viewers to "Be on the lookout for Andrew Hughes, an American." Andrew Hughes is the name of one of the other actors. He is the older gentleman playing Dr. Stevenson.
This is only the second film in the Godzilla series up to this point since Godzilla (1954) in which Godzilla himself actually appears in or attacks Tokyo. In Le Retour de Godzilla (1955) Godzilla appears in Osaka, in King Kong contre Godzilla (1962) he never actually makes it to Tokyo, in Mothra contre Godzilla (1964) he appears in Nagoya, in Ghidrah, le monstre à trois têtes (1964) he appears in Yokohama, in Invasion Planète X (1965) he is taken from Lake Myojin by the Xiliens and then appears in the Nagano Prefecture, while Ebirah contre Godzilla (1966) and La Planète des monstres (1967) both take place on two fictional South Pacific islands.