Seventeen years after the war with the Crystals had begun, the Vanquish Crystal Defense, or VCD, is awaiting orders to launch the Fighting Thunders into battle to assist the North American army which is being attacked by the Crystals. Aboard the VCD flagship, the Bellwether, Richard "Max" Maxwell and Eshiria Portman lament that they are being held back during what they consider a Crystal contamination far bigger than the other problems the VCD had experienced.
Eventually, after receiving the long-awaited attack order to assist the North American army and destroying Platon, a battleship contaminated by the Crystals, Max and Eshiria receive word from the Middle East branch of the VCD that there is major Crystal activity in the region. Eshiria notes that the energy signatures detected in the region are the same as the one in North America. The crew stumbles upon a cave full of Crystals, and Max has a shipment of the Crystals send to the French shipping port, under suspicion that the Crystals have a sign of intelligence. Max then issues an SOS call to the port after the Fighting Thunder destroys the contaminated drilling machine Great Horn inside the cave, even after having doubts from his superior, Helga Lindenbaum of the international peace council. The suspicion is unfortunately proven right, as the Crystals are attacking the port. Max also realizes that the Crystals have the ability to upgrade any machinery they contaminate, as demonstrated by the submarine Kraken transforming into a hovercraft.
Max orders Fighting Thunder on a mission to the Large Hadron Collider facility, expecting a massive Crystal presence there. His suspicions are again proven right, as the Crystals have laid siege to the facility in an orderly military fashion with Max hypothesizing that there may be a core relaying orders to the Crystals. After clearing the contamination at the LHC facility and thwarting the threat posed by the mounted cannon carrier Spice Birds, a surveillance drone detected on the Bellwether's deck steals the Crystals and delivers them to a pirate mercenary named Valbarossa Hawkeye, who plans on sending the Crystals to an unknown facility.
Max then sends out Fighting Thunder to pursue Valbarossa and retake the Crystals. Valbarossa detects Fighting Thunder and orders the flagship to attack. As Valbarossa's ship's defenses are being disabled, the stolen Crystals suddenly start to contaminate the ship's command bridge, the Blow of Hornet, and upgrade it with an energy cannon to destroy Fighting Thunder. After destroying the contaminated pirate ship, Valbarossa, revealing herself to be a woman, joins Max and Eshiria aboard the Bellwether.
Valbarossa reveals her client to be Lieutenant Walter Erick Campbell, head of VCD's weapons development division and a researcher in the organization SHIFT. VCD locates the SHIFT facility where Campbell is located, and orders Fighting Thunder to raid the facility. Earlier, Campbell had reminded Max that it was the efforts of SHIFT and utilizing Crystal energy that are the reasons why the Fighting Thunder project and the Bellwether exist, and that the war effort is dependent on him. During the raid on the SHIFT facility, Campbell reiterated his stance on SHIFT's continued research, denouncing the Montevideo Agreement that had banned the research on Crystal technology, but Max says that since he is on the front lines, he knows how dangerous the Crystals are, since the Crystals had contaminated Valbarossa's pirate ship. After destroying the facility, Fighting Thunder begins to escape through the cargo route, but not before Campbell sends out mobile weapons Messiah out of spite against Max and Fighting Thunder.
Following the attack on the SHIFT facility, Helga confirmed Max and Eshiria's hypotheses of the Crystals, culminating in the conclusion that one of them is relaying information on the other Crystals and the machines they contaminated, comparing it to Carl Jung's theory on the collective unconscious. Helga then orders Max and Eshiria to leave Earth's atmosphere to launch a counteroffensive on the Crystals and their mother planet, not before founding out that the space debris removal colony Angel was too contaminated and must be destroyed.
Upon arriving at the Crystals' home planet, Max and Eshiria notice that there are no signs of life to be found on the planet and is completely overrun by the Crystals. Detecting large energy signatures underground, they order Fighting Thunder to infiltrate the interior of the planet and investigate, which confronts a spherical being that appears to be the planet's guardian, Humpty Dumpty. During the battle, Eshiria discovers that the atmospheric composition of the planet is the same as Mars. The data Fighting Thunder relayed to the Bellwether reveals that the large Crystals are made up of the same composition as water, and that the Crystals' invasion of Earth was not a normal invasion at all. Their true motive was to reset Earth by annihilating all life on the planet through pollution and contaminating their weapons and machinery before cleaning up the pollution and making the planet habitable again.
Depending on the player's performance, the game will end with either VCD returning home after the offensive against the Crystals' homeworld and see what looks to be Mars, only to find that it's Earth reduced to a lifeless red rock by the Crystals, or the Bellwether unable to return to Earth due to damages sustained by the Crystals during the final battle, but with the Earth celebrating their victory against the Crystals as a result of the destruction of the enigmatic crystalline core Divine Rampart, and Crystals themselves melt into liquids forming rivers and seas in their home planet, Helga sends in a rescue ship for the crew that will arrive within a month, and Max cautions to stay vigilant in case of another attack in the future.
