According to former Rare developer Kevin Bayliss, Jago's ripped trousers were inspired by those worn by Def Leppard's lead singer Joe Elliot, particularly those seen in the 1989 concert film Live: In the Round, in Your Face.

Killer Instinct was originally titled "Brute Force", with the name being changed much later in development, along with that of most of the characters. All of the characters except for Jago, Glacius, and Eyedol went through at least one name change over the course of development.

There are two unused voice clips in the game's files, announcing characters named "Heatshade" and "Pyrotech". These were intended for the character select screen and were early names for Cinder.

The original Killer Instinct arcade game calculates the damage inflicted on an opposing player through a random number generator. Generally, light attacks cause 3-6 points of damage while heavier normals range between 15-19. The value for causing a dizzy state, however, remains a constant.

Sabrewulf was originally planned to transform back into his human form as a weakness.

As part of a licensing deal between Midway and Nintendo, the arcade versions of Cruis'n USA and Killer Instinct were advertised both in their attract modes and on flyers as being powered by Nintendo's Ultra 64 hardware, which would eventually be released as the Nintendo 64. However, this claim was false; the versions of both games shown at the 1994 Summer Consumer Electronics Show ran on a modified JAMMA arcade board. As for the versions released to arcades, Cruis'n USA ran on the significantly different Midway V arcade hardware, while Killer Instinct only utilized parts of the Nintendo 64 hardware. It used a 64-bit MIPS CPU and the Nintendo 64 file format for data structure, but not the console's memory media or graphics technology.