At the end of Spoiler:Catwoman/Cyborg's Chapter, Spoiler:Catwoman will say the Brother Eye override authorization code, "LK-4D4", a reference to Mortal Kombat's Cyrax.

Hitting the opponent into the movie sign in the Gotham City stage enough times will have the letters spell out "FINISH HIM" and darken the background. A reference to Mortal Kombat, another title from NetherRealm Studios

Both Superman and Batman's "Super Moves" are a reference to their own Hollywood films.
When Superman performs his "Super Move" he'll beat his opponent in the sky, the same way he did with General Zod in their final battle from "The Man of Steel". And when Batman performs his "Super Move", he'll summon the Batwing to drag his opponent up to the sky, pausing in front of the moon to make the Batman symbol, the same way it did in Tim Burton's 1989 Batman movie, when Batman fought against the Joker.

In one of Harley Quinn's introduction lines to Mr. Freeze, she asks if he can "make her a pony", to which he retorts, "It will make the twilight sparkle." Harley Quinn then will say, "Hahahaha! I was hoping you'd say that." This is a reference to Harley Quinn's voice actress, Tara Strong, who also voices Twilight Sparkle in the series "My Little Pony: Friendship is Magic".

At one point, NetherRealm Studios considered making a Fighter Pack 0, consisting of characters from Injustice: Gods Among Us, e.g. Ares, Batgirl, Doomsday and Shazam, however the idea was scrapped.

When Injustice 2 launched, the Mr. Freeze's premiere skin was missing its helmet. It was given a helmet in the June 2017 update of the game.

When performing the stage transition on the Atlantis stage, Black Manta makes a cameo appearance. Strangely, even if the player chooses Black Manta, Black Manta will still appear.

In a clash quote with Joker and Black Adam, the former will ask if he met "that other lightning guy?" and the latter will respond by saying "With the bamboo hat? Yes." A reference to Raiden from Mortal Kombat.

At one point, Static, from Static Shock, was going to be considered for the roster, but he ultimately didn't make the cut.

When Raiden wins a round, there is a chance that he will summon Kidd Thunder, a reference to his Friendship victory in Mortal Kombat II

When any one of Teenage Mutant Ninja Turtles lose a match, there is a chance they will sit on the ground as stars spin above their head in reference to Teenage Mutant Ninja Turtles: Turtles in Time.

When Scarecrow wins a round, there is a chance he will say, "Now I'm playing with power", a quote said by Freddy Krueger in Freddy's Dead: The Final Nightmare. Robert Englund, the voice actor for Scarecrow played Freddy Krueger in said film.

When you finish a match with one of the Teenage Mutant Ninja Turtles, they will throw a pizza on the screen, a reference to the intro in the 1987 cartoon where Raphael throws a Pizza to the screen.

One of Captain Cold’s Combos is called “Prison Break”, a reference to the TV show of the same name.

In an intro dialogue with Michelangelo and Atrocitus, after Atrocitus says that he "could wear a red ring", Michelangelo will reply back saying how he "should have worn the red bandana." A reference to how Michelangelo wore a red bandana in the original Mirage Comics.

In June 2021, the game's developer NetherRealm issued an apology after it received backlash from the community over its special event in celebration of Pride Month in the mobile port of Injustice 2. The event's challenge was for players to defeat Poison Ivy, a character which identifies as bisexual, hundreds and thousands of times to unlock prizes, a task which was deemed to be tone-deaf by the community.

In their apology, they stated, "We recognize associating our latest Global Challenge with Pride was insensitive and inappropriate. Real life violence against the LGBTQIA+ community and women within that community in particular is all too common and we should actively engage in efforts to end LGBTQIA+ violence, not normalize it. We apologize to the greater community, but especially LGBTQIA+ members. We are committed to listening and doing better."

During Game Informer's 166 rapid-fire question interview with Ed Boon about Mortal Kombat 11, it was mentioned that Neo from The Matrix almost became a combatant in Injustice 2 but the deal fell through.