In the near future, mankind was driven away from the seas and landmasses were isolated from each other with the advent of the "Fleet of Fog", All controlled ships which destroyed all opposition turning the world into turmoil. Years later, the Japanese Government is about to launch an unmanned cargo shuttle into orbit when the Fleet of Fog ship Nagara appears to prevent it. The launch is a success when the human-crewed Fog submarine I-401 defeats the enemy by request of the government. After the battle, the I-401's captain Gunzō Chihaya reminisce with its mental model, a human-shaped avatar called Iona about their first meeting two years ago. It was during this time that I-401 was under human custody for years, but unresponsive until Gunzō comes in contact with it, awakening Iona. After Iona reveals that she had instructions to serve under him, Gunzō agrees to join forces with her, and they flee together. Back to the present, Gunzō is approached by Ryūjirō Kamikage, the Assistant Secretary of Military Affairs, who reveal that the shuttle was destroyed before accomplishing its task, which is to deliver the plans of a new weapon developed to fight the ships of the Fog to the United States, as Japan now lacks the resources needed to mass produce it. Accepting the task of crossing the Pacific Ocean to take the plans to the US by themselves, Gunzō and his crew depart to resupply at the Yokosuka Base, but the Fog's Heavy Cruiser Takao takes heed of the I-401's approach and prepares itself to engage it.

Takao blocks the I-401's path to Yokosuka by positioning itself inside the eye of a typhoon and after asserting that any attempts to avoid confront are too risky, Gunzō decides to take Takao head on. After Iona barely evades an attack from Takao's Super Gravity Cannon, Gunzō analyzes the combat data so far and points out that Takao's attacks have had pinpoint accuracy from a distance much greater than its usual sensor capabilities and concludes that it is only possible by having a submarine concealed directly under its hull. Gunzō then orders the crew to ready their own Super Gravity Cannon which they salvaged from their previous battle with the Fog ship Hyūga and uses it to destroy the submarine and force Takao to surrender. Having her systems locked down for 24 hours by Iona to prevent her from give chase to the I-401, Takao wonders about the reasons why Gunzō spared her and takes an interest on him.

The I-401 and her crew reach the Yokosuka Base for repairs and resupply, and Gunzō takes Iona for a visit to Navy memorial for those that died in the war against the Fleet of Fog. Soon after, they are taken against their will by the Japanese Army with the rest of the crew to meet Ryōkan Kita, a former member of the Navy and an influential politician who attempts to convince Gunzō to relinquish the I-401 to the Japanese Army with no success. Meanwhile, Takao is approached by the mental models of Fog surveillance submarines I-400 and I-402 and reveals her intentions to abandon the fleet and join Gunzō's side. However, she is informed by them that two Fog battleships were dispatched to sink the I-401 and Takao leaves, claiming that she will wait for Gunzō at another location. When the Yokosuka port is under attack by said battleships, Haruna and Kirishima, Gunzō and his crew return to their submarine, subduing all resistance from Kita and his men and prepare themselves to confront the new enemies before them.

The battle against Haruna and Kirishima begins with the I-401 drawing them to a trap they set at the ruins of the old Yokosuka city, which fails to damage the enemies but allows them to circle around them undetected and launch a surprise attack using the now sunk Japanese battleship Mikasa as a decoy. However, Kirishima prevents being hit in the nick of time and launches a barrage of warheads at them, which they barely manage to avoid. To finish the I-401 for good, Haruna and Kirishima combine together to generate a huge gap in the water and trap it into the line of fire of their Super Gravity Cannon, but just before firing at Iona, they leave themselves vulnerable to her last Erosion Torpedo concealed inside Mikasa's wreckage that triggers a chain reaction destroying both ships, although Haruna's mental model manages to salvage Kirishima's core and escape. In the next day, a child finds the unconscious Haruna inside an abandoned warehouse.

The I-401 returns to Yokosuka to pick up the secret weapon developed by the Japanese Government, the "Vibration Warhead", before returning to their base at Iwo Jima to make the final preparations for its journey across the Pacific. Meanwhile, Haruna awakens and meets Makie Osakabe, the child who rescued her. Pretending to be a human, Haruna keeps Makie company while Kirishima's core uses some of her nanomachines to make a spare body for her out of a Teddy bear. Takao arrives at Iwo Jima ahead of I-401 but is stopped by a vicious attack from unknown origin. Realizing that Makie is related to the deceased Tōjūrō Osakabe, the creator of the Vibration Warhead, Haruna and Kirishima contact their flagship Kongou and are instructed to investigate further. In the occasion, the two mental models are introduced to Tōjūrō, who is revealed to be alive, but bedridden. Tōjūrō reveals that after several failed attempts to develop a weapon to counter the Fleet of Fog, he came with a plan to create an artificial being with superior intellect capable to succeed where he did not, and the only surviving offspring of said project is Makie, who was the true creator of the Vibration Warhead. To protect Makie from the government, Tōjūrō forged his death and kept watching over her from the shadows but knowing he has not much time left and seeing how attached she became to them, he asks Haruna and Kirishima to take care of her. However, the army is already aware that Makie had made contact with ships of the Fog, and sends a unit to dispose of her.

As Tōjūrō passes away, Haruna decides to protect Makie and asks Kirishima's help for it. Despite facing some heavy opposition, Haruna refrains from killing the attackers and orders Kirishima to flee with Makie, while she creates a decoy with her nanomachines to draw the military's attention. However, the soldiers see through Haruna's trick and start searching for Makie who is distraught with learning that she created a weapon that can destroy Haruna. Once reunited, Haruna, Kirishima and Makie are driven to a corner when Haruna asks for anyone's help, and Iona answers her call. Gunzō is contacted by Kamikage and replies to him that the I-401 and its crew were hired just to deliver the vibration warhead to the US and beside it, they will do as they please. Once the army retreats, Iona takes the three of them to the submarine and Haruna asks Makie to become her and Kirishima's friends to which she agrees. As the I-401 departs for Iwo Jima, Takao awakens in a room, greeted by a mysterious voice who asks for her intentions.

Taking Haruna, Kirishima and Makie with them, the I-401 and its crew arrive at their base in Iwo Jima, where they are greeted by the fast battleship Hyuga's mental model who was guarding the island for them, and much by their surprise, they meet Takao once again. As Hyuga make repairs on I-401, Gunzō and his crew prepare to abandon the base as there are not much supplies left and they know that delivering the vibration torpedo to the United States may ensure their objective, which is to put mankind and the Fog on equal terms, which may lead to the end of the blockade. By Hyuga's suggestion, Takao considers joining Gunzō and the others' side while Haruna and Kirishima are contacted by Kongou who asks for their intentions. While Haruna affirms that she will not return to the Fleet of Fog for Makie's sake, Kirishima claims that she will continue by their side for the sake of gathering info. Kongou then assembles her fleet and prepares an assault on Iwo Jima.

With Iwo Jima surrouded by the enemy fleet, Hyuga makes contact with Kongou by Gunzō's request, asking for a meet in private with her mental model before they begin hostilities. Kongou answers her call and she rendezvous with them at the beach, accompained by the Heavy Cruiser Maya. As the rest of the crew remain on standby aboard the I-401, Gunzō discuss with Kongou and the other mental models about the real intentions of the Fleet of Fog and learns from her that she and the other ships have only one purpose, which is to follow the "Admiralty Code" that instructed them to chase the humans away from the seas and prevent all contact overseas between them. Instead of discussing the matter further, Gunzō invites the guests for a barbecue at the beach where Kongou asks Iona about the reason why all ships who come in contact with her start displaying a behavior independent from the Admiralty Code, but when she refrains from responding, Kongou claims that she will not fall by their trap and it is revealed that both her and Maya's mental models are actually decoys, with their cores being safely guarded at their respective ships to prevent them from being influenced by human behavior, before they begin to attack. Hyuga has a hard time defending the island against the enemy barrage until Takao, Haruna and Kirishima step in to assist her. Disappointed that he and Kongou could not see eye to eye, Gunzō declares that it's up to him to find a way past her and deliver the vibration torpedo to the United States.

Hyuga stays behind deflecting the attacks of Kongou's fleet to buy time for Iona and the others to escape. Before leaving Iwo Jima, Gunzō asks for Takao's help and she agrees to join his side. Unwilling to listen to Hyuga's words, Kongou fires her Super Gravity Cannon at her but fails to destroy her and taking advantage of her getting exausted, orders Maya to fires her own cannon but Takao appears in the nick of time to block Maya's shot. Believing that Hyuga and Takao are just covering the I-401's escape, Kongou tracks her down and gives chase, refusing to slow down even after falling into a minefield left by Hyuga to help Iona escape. Iona tries to reason with Kongou with no success and when the battleship attempts to fire her Super Gravity Cannon underwater to sink her, Hyuga manages to hack into Kongou's systems to have her lose control for time enough to Iona and Gunzō to escape. Takao then reveals to Kongou that instead of Takao, the true decoy was Iona herself, while the vibration warhead, Makie, her friends and the rest of the I-401's crew were safely hidden aboard her and she returns to pick up Hyuga to rendevous with Iona and Gunzō, who despite escaping from Kongou's grasp, are ambushed by I-400 and I-402 and apparently sunk by them.

With her nanomaterials compromised by her sister ships attack, the I-401 sinks into the deep ocean while Iona tends to an injured Gunzō. Meanwhile, Takao and the others look for them but all communications and radar are jammed by spatial distortions from the last battle. Despite knowing that the only way for her to survive is to abandon her captain, Iona refuses to do so until Gunzō orders her to cut all life support systems, claiming that fulfilling their mission to deliver the vibration warhead is more important than saving him. However, when Gunzō stops responding, a distraught Iona breaks down her own mental model to create a survival pod for him and her core. When Takao locates the pod, she decides to sacrifice her own body and use its nanomaterials to restore Iona and the I-401, bringing them back to surface and saving Gunzō's life. Once knowing that the I-401 has not perished, Kongou can't hide the urge to fight it again, but declaring that she is displaying the same erratic behavior seen in the other ships who deviated from the Admiralty Code, I-400 and I-402 relieve her from duty and lock down her systems. In the occasion, Kongou finds out that Maya's mental model lacks conciousness, being an artificial intelligence created just to watch over her.

On their way to Hawaii, their next stop of their journey to deliver the vibration warhead in San Diego, the restored and upgraded I-401 is chased by several Nagara class ships that are surprised and sunk when Gunzō orders an unexpected maneuver to sweep them all at once. After the battle, it is revealed that despite losing her physical body, Takao's core is still intact and she is now part of the I-401's systems. However, knowing that they are still being followed by I-400 and I-402, Gunzō decides to confront them. Before the battle, Iona's sisters make contact with her asking for her true intentions but she claims it is too difficult to explain with words. Meanwhile, an imprisioned Kongou breaks free and absorbs Maya along all the other ships arround her. To confound their enemies, the I-401 moves forward along two decoys with increased capabilities, thanks to Hyuga, Haruna and Kirishima's direct control over them. After exchanging some fire, Iona contacts her sisters asking them to stop pursuing them before it is too late but they refuse to comply. When I-400 is about to be stricken by surprise, I-402 sacrifices herself to protect her sister, who despite finding this decision illogical, becomes driven into anger, leading her to fall into a trap set by the decoys and her defeat as well. Despite grieving for her lost sisters, Iona maintains her resolve to follow Gunzō to the end. However, the I-401 is soon after approached by a dozen ships from the American Fleet of Fog at the front, and a massive flying object at the back, composed of several fused ships led by Kongou, who claims that she wlll be the one who will sink I-401.

Kongou obliterates the ships of the American Fleet of Fog and Iona, along the other mental models, make contact with Kongou in an attempt to bring her to her senses. However, Kongou claims that it's her duty to prevent further anomalies to the Fog by destroying Iona and all ships who come in contact with her, including herself, before locking down all communications. After barely deflecting an attack of Kongou's enhanced Super Gravity Cannon, the I-401 conceals itself, knowing that confronting her directly is useless, when Iona decides to reach Kongou and confront her face to face. Gunzō agrees with her plan and after evading a massive barrage of attacks, Iona boards a torpedo to reach Kongou's deck. Iona attempts to reason with Kongou who keeps attacking her until she finally traps Iona and prepares to self destruct herself to kill both, when the sequence is disrupted by I-401's Super Gravity Cannon. In the end, Iona suceeds to dissuade Kongou and prevents the destruction of both. The reformed Kongou befriends Iona while the superstructure created by her collapses. Days later, as the I-401's crew delivers the vibration warhead to the U.S. Navy as intended, Takao's body is restored and they return to the sea, hoping that their actions have helped change the world for the better.