The evil emperor Shao Kahn opens a portal from Outworld to the Earthrealm and has reclaimed his queen Sindel, who is Kitana's long-dead mother. With the portal open, Earthrealm is in danger of being absorbed into Outworld within six days, a fate which Liu Kang and the others must fight to prevent. Johnny Cage (Chris Conrad) is killed by Kahn during the confrontation, and the remaining Earthrealm warriors must regroup. Raiden goes to ask the Elder Gods why Kahn was allowed to break the rules of Mortal Kombat.

Sonya enlists the help of her old partner, Jax. They are ambushed by a group of Kahn's warriors, led by the cyborg Cyrax, all of whom are eventually defeated. Meanwhile, Kitana and Liu Kang search for a Native American shaman named Nightwolf, who they have been told knows the key to defeating Kahn. On the way, they run afoul of the cyborg Smoke. Kitana and Liu Kang dispatch of him with the aid of Sub-Zero, the younger brother of the Sub-Zero whom Liu Kang had defeated in the previous tournament. Sub-Zero agrees to help Kitana and Liu Kang, but Scorpion suddenly appears, attacks Sub-Zero, and kidnaps Kitana. Knowing that Liu Kang is not yet strong enough to face Kahn, Sub-Zero exhorts him to continue on to Nightwolf before pursuing Scorpion and Kitana, then disappears.

Raiden meets with the Elder Gods and asks them why Kahn was allowed to break tournament rules and force his way into Earthrealm, and how he can be stopped. The answers he receives are sparse and ambiguous; One Elder God says that reuniting Kitana with her mother, Sindel, is the key to breaking Kahn's hold on Earthrealm, but another Elder God insists that the defeat of Kahn himself is the solution. Raiden is then asked by the Elder Gods about his feelings and obligations towards the mortals, and what he would be willing to do to ensure their survival.

Liu Kang finds Nightwolf, who teaches him about the power of the Animality, a form of shapeshifting which utilizes the caster's strengths and abilities; essential if Liu Kang is to defeat Kahn. To achieve the mindset needed to acquire this power, Liu Kang must pass three tests. The first is a trial of his self-esteem and focus. The second comes in the form of temptation, which manifests itself in the form of Jade, who attempts to seduce Liu Kang and make him forget about Kitana. Liu Kang resists Jade's advances, which impresses her. She offers her assistance in fighting Kahn. Liu Kang accepts Jade's offer and takes her with him to the Elder Gods' temple, where he and his friends are to meet Raiden.

Sonya and Jax also head to the temple, only to be confronted by Mileena, who Sonya initially mistakes for Kitana, and an unearthly creature. Jax and Sonya defeat their adversaries and continue towards the temple. At the temple, the Earthrealm warriors reunite with a newly-shorn Raiden, who explains that he has sacrificed his immortality to freely fight alongside them. Together, they head for Outworld to rescue Kitana and reunite her with Sindel.

With Jade's help, Liu Kang sneaks into Kahn's castle and rescues Kitana, while Raiden, Jax, and Sonya find Sindel. Unfortunately, Sindel remains under Kahn's control, and she escapes while a trio of Raptor warriors ambush the heroes. Jade also steals away, having revealed herself to be a mole sent by Shao Kahn to disrupt the heroes' plans. Raiden then reveals that Shao Kahn is his brother, and that Elder God Shinnok is their father. He realizes that Shinnok had lied to him and is supporting Kahn. With renewed purpose, Raiden and the Earthrealm warriors make their way to the final showdown with Kahn and his generals.

Liu Kang and his friends openly challenge Kahn and his allies, only to be interrupted by Shinnok, who demands that Raiden submit to him and restore their broken family, at the expense of his mortal friends. Raiden flatly refuses, and is killed by an energy blast from Kahn.

Though the early going is rough, Jax, Sonya, and Kitana emerge victorious against their opponents. Liu Kang has a much more difficult time, however, battling against Kahn; he manages to tap into his Animality but he is barely able to hold his own against Kahn's own Animality. Shinnok in turn prepares to wipe out Liu Kang, but two of the Elder Gods intervene, having uncovered Shinnok's treachery. They declare that the fate of Earth shall be decided lawfully, through Mortal Kombat. Kahn taunts Liu Kang, angering him enough to give him a second wind. Liu Kang defeats the Outworld Emperor once and for all, and Shinnok is banished to the Netherealm by the other Elder Gods.

Earthrealm reverts to its former state, and Shao Kahn's hold over Sindel is finally broken, allowing her to reunite with Kitana. Raiden is revived by the other Elder Gods, who bestow upon him his father's former position. With everything right in the universe once again, the Earthrealm heroes return home triumphant.