Following Shinnok's defeat, Dark Raiden plans to protect Earthrealm by destroying all of its enemies and making an example of Shinnok; decapitating him. This latter act inspires Kronika, Shinnok's mother and the keeper of time, to rewrite history to undo Raiden's interference and erase him from existence. Two years later, a Special Forces strike team led by Sonya Blade, Cassie Cage, and Jacqui Briggs attack the Netherrealm, with Raiden providing assistance. The team succeeds in destroying the Netherrealm castle, though at the cost of Sonya's life. Kronika forms an alliance with revenants and Netherrealm's rulers, Liu Kang and Kitana, immediately afterwards.

Meanwhile, Kotal Kahn, the current emperor of Outworld, attempts to execute Shao Kahn loyalist Kollector, but is interrupted by a time storm that brings Shao Kahn, Skarlet, Baraka, and younger versions of Kano, Erron Black, Jade, Raiden, Kitana, Liu Kang, Johnny Cage, Sonya, Jax, Scorpion, Kabal, and Kung Lao from the past and erases Dark Raiden from existence. A battle erupts in Kotal's Koliseum until D'Vorah transports Baraka, Kollector, Skarlet, Shao Kahn, Black, and Kano to her hive, recruiting them into Kronika's fold.

Liu Kang, Kung Lao, and Raiden appear at the Earthrealm's Special Forces HQ after forging an alliance with Kotal while Jade and Kitana aid Kotal in protecting Outworld from Kronika's forces. Liu Kang and Kung Lao investigate the Wu Shi Academy and encounter Kronika's right-hand man, Geras. Their subsequent battle ends with Geras using his chronokinetic powers to escape with powerful energy capsules containing Earthrealm's life force.

The Special Forces learn that Sektor, backed by Noob Saibot and a cyberized Frost, has reinstated the Cyber Lin Kuei to build an army of cyborgs out of kidnapped Lin Kuei warriors for Kronika. Grandmasters Sub-Zero and Hanzo Hasashi shut down Sektor's factory with Cyrax's aid, forcing Geras, Black, and both versions of Kano to retreat to Kronika's Keep, where they revive Sektor and rebuild the cybernetic army themselves.

Meanwhile, Raiden tries to consult the Elder Gods. They cannot intervene as the time storm is draining their power, but Shinnok's twin sister Cetrion gives him a clue on how to defeat Kronika. During a later attempt, Raiden discovers Cetrion had betrayed and killed the Elder Gods to serve her mother: Kronika. Kotal and Jade go to a Tarkatan camp to ask for their help fighting against Shao Kahn, but Kotal's hatred towards the Tarkatans causes Jade to battle him before Shao Khan appears and captures him.

The Special Forces base is destroyed by the Black Dragon gang and Kronika's cybernetic army, with the younger Johnny and Sonya captured, the elder Johnny wounded, and Sektor self-destructing in the process. Due to this and the destruction of Sub-Zero's Lin Kuei Temple and the Wu Shi Academy's Sky Temple, Earthrealm's heroes reconvene at Hasashi's Fire Garden. Cassie leads a strike team to save her parents, where Sonya kills the younger Kano to erase his present self from existence. Meanwhile, Kitana, Liu Kang, and Kung Lao battle Baraka to secure an alliance between him and Sheeva. With their aid, Kitana successfully defeats and blinds Shao Kahn,[15] uniting the Outworld factions and inheriting the throne from Kotal.

Raiden sends Jax and Jacqui to Shang Tsung's now-abandoned island to retrieve the Crown of Souls, but the pair are thwarted by Cetrion, who eventually escapes with the Crown, and present-day Jax, who had been deceived by Kronika into helping her in exchange for averting his time as a revenant. Hasashi is tasked with convincing Kharon, the ferryman of Netherrealm's souls, to join their side so they can travel to Kronika's fortress. Hasashi fights Scorpion and persuades him to join his side, but is fatally wounded by D'Vorah. Scorpion drives her away and returns to the Fire Garden to honor Hasashi's dying wish. Refusing to believe him, Raiden attacks him on sight using Shinnok's amulet. Liu Kang intervenes, causing Raiden to realize how they have fought before across multiple timelines and that Kronika had orchestrated them all because she fears their combined strength. Anticipating this, Kronika kidnaps Liu Kang. With Kharon recruited, a joint Earthrealm-Outworld army assaults Kronika's Keep. Geras is dropped in the bottomless Sea of Blood; Frost is shut down, disabling the cyber Lin Kuei; and the present Jax defects to the heroes' side.

Once revenant Liu Kang has absorbed his past self's soul, Kronika sends him to attack Raiden, who eventually merges with him to become Fire God Liu Kang. The heroes breach Kronika's Keep, but Kronika turns back time. With his god-like status making him immune, Liu Kang defeats the remaining revenants and Cetrion. Kronika then absorbs Cetrion's essence to strengthen herself enough to reverse time back to the primordial state of the universe, erasing all the events in the franchise from existence. Fire God Liu Kang is left unaffected due to his godly status. Kronika and Fire God Liu Kang fight one final time to determine the fate of the New Era.

Depending on the outcome of the battle, the epilogue will show one of the following:

Following Kronika's defeat, Fire God Liu Kang and Raiden attempt to utilize Kronika's Hourglass to restore history, but are interrupted by Shang Tsung, Fujin, and Nightwolf, who were all imprisoned in a timeless void by Kronika for refusing to join her. Shang Tsung elaborates that, due to the destruction of the Crown of Souls when Liu Kang defeated Kronika, the Hourglass cannot be used to change history without destroying it. He convinces Liu Kang to send him, Fujin, and Nightwolf back in time to retrieve the Crown of Souls before Cetrion does. Despite Raiden's suspicions of Shang Tsung, Liu Kang agrees and sends the trio back, staying behind to protect the Hourglass.

Shang Tsung, Fujin, and Nightwolf are transported to the Koliseum just as Kitana confronted Shao Kahn. They attempt to flee undetected, but news spreads of their arrival, prompting Kronika to retaliate. To face Cetrion on his island, Shang Tsung determines their best option is to resurrect Sindel, so they head to the Netherrealm and capture her revenant. Returning to Outworld, Shang Tsung uses Sheeva's blood debt to Sindel to gain access to the Soul Chamber and restore Sindel despite fierce resistance from Kitana, Jade, Kotal, Black, and Baraka.

Sindel accompanies Shang Tsung and the others to his island, where Fujin defeats Kronika's forces and convinces present-day Jax to defect early while Sindel defeats Cetrion and helps the group capture the Crown. Fujin and Shang Tsung travel to the Fire Garden to convince Raiden of Shang Tsung's alliance. When Kronika attempts to intervene, Raiden, Fujin, and Shang Tsung fend her off, though she reveals the sorcerer was the one who designed the Crown.

As the offensive on Kronika's Keep is about to commence, Shang Tsung signals Sindel to heal Shao Kahn. The pair then betray and defeat Sheeva, gaining control of her army before destroying Geras, imprisoning the Cage family, defeating Kitana, Liu Kang, and Jade, throwing Kung Lao into the Sea of Blood, and killing Kotal. It is revealed that Sindel was never brainwashed and had willingly married Shao Kahn after he conquered her realm by killing her former husband and Kitana's biological father. While Fujin spearheads the offensive on Kronika's Keep, Raiden discovers Shang Tsung's plot and Sindel's betrayal while fighting revenant Liu Kang when the latter receives injuries from his past self.

Raiden arrives too late to stop Shang Tsung from tricking Fujin into giving him the Crown. The sorcerer gains Kronika's full power, revealing he had planned everything after Kronika imprisoned him. He overpowers and drains Raiden and Fujin's souls before using Sindel and Shao Kahn to reach the Hourglass. Once Kronika's remaining revenants are killed, Shang Tsung betrays Sindel and Shao Kahn and takes their souls as well before defeating and erasing Kronika from existence, gaining the last of her power. As he starts approaching the Hourglass, Fire God Liu Kang appears, revealing he was aware of Shang Tsung's intentions and, knowing he was the only one strong enough to defeat Kronika, allowed Shang Tsung to stay alive to protect the Crown.

From this point, the player can choose their "final destiny" and fight as Shang Tsung or Liu Kang. Depending on the outcome of the battle, the story ends in one of the following outcomes: