Despite being the eighth mainline game in the series, in relation to Mortal Kombat's continuity, the game's events are considered a non-canon "What If?" scenario placed in-between the events of Mortal Kombat II and Mortal Kombat 3 and not as a sequel to Mortal Kombat: Armageddon, despite featuring characters from later entries such as Quan Chi. Regardless, the events of the game are referenced in Injustice 2 and Mortal Kombat 11. In the case of the latter game, which establishes a multiverse for the series, it is implied the events of the game took place in another timeline.

Before becoming a crossover, the game was originally planned to be a darker reboot of the series under the title "Mortal Kombat 8", inspired by games of the era like Gears of War and taking advantage of Unreal Engine 3. During the planning process however, Midway managed to acquire the DC Comics license, transforming the game into the crossover. The pitch of the game stimmed from series creator Ed Boon always wanting to do a crossover game with another franchise, naming Street Fighter among potential candidates, and so they could have an opportunity to explain why Mortal Kombat and DC Comics characters were fighting each other in the first place, as opposed to Marvel vs. Capcom which Midway senior producer Hans Lo described as "random". Despite this, the game is still considered the eighth mainline Mortal Kombat game.

Leftover data for Brainiac can be found within the game's files, suggesting he was going to be added to the game, but never was.

In the PAL version, Deathstroke shot his opponents on screen in his fatality move, but was cut off screen in the NTSC version.

After Captain Marvel's last opponent in the DC Storyline, The Joker references a scene from Star Trek II: The Wrath of Khan. After hearing the news of Dark Kahn, he looks up to the sky and yells "KAHN" similar to Captain Kirk.

Quan Chi and Harley Quinn were two characters who were originally announced to be added to the game as potential DLC, but due to Midway's bankruptcy, they were never released. Prototype assets for Harley Quinn were later leaked in 2025 as part of a dump of beta content from hundreds of Xbox 360 games.

The Joker's first Fatality shows him shoot a fake gun at his opponent, followed up by shooting them in the head with a real gun. To maintain a T rating from the ESRB, the US version was censored by focusing the camera away from the opponent as they were shot. The UK version shows the full uncut version of the Fatality.