After the Earth was destroyed by mysterious alien lifeforms known as the Gauna, surviving remnants of the human race escaped to space in the enormous generation ship Sidonia. Having drifted through space for millennia, the Sidonia found itself once more under attack from Gauna for the first time in a century. Once again facing the threat of extinction, a temporary victory against the Gauna was eked out thanks to the human-Gauna hybrid Tsumugi Shiraui and ace Guardian mech pilot Nagate Tanikaze. 10 years later... The people of Sidonia enjoy a brief respite. Peaceful days pass, during which Tsumugi begins to realize her feelings for Nagate, who is now celebrated as a hero of Sidonia. However, as Captain Kobayashi has always known, as long as the Gauna remain, peace cannot last. The decision is made: a final battle, upon which rests the fate of humanity's last survivors. As the end approaches, will the crew be able to protect those they love? (Source: Polygon Pictures)

After barely escaping a collision with a gigantic Gauna at the cost of many human lives, Kobayashi—the captain of the spaceship Sidonia—is prompted to change her political paradigm. Once she seizes full power, Kobayashi aims to eradicate the Gaunas from the Lem system where former Sidonians have recently established a colony. Her ambition is justified by two breakthroughs: the development of highly effective, long-range anti-Gauna weapons, and the creation of Tsumugi Shiraui—the first human-Gauna chimera possessing great destructive power. Facing hostility toward chimeras and her uncertain large-scale military expedition, Kobayashi enlists the help of the new elite pilot Nagate Tanikaze. Due to his personal experiences with Shizuka Hoshijiro and Benisuzume's placenta, Tanikaze soon develops a close bond with Tsumugi. As the final battle against humanity's most formidable opponent approaches, Tanikaze tries to enjoy the last days of peace with his friend Izana Shinatose—all while Kobayashi secretly pursues the development of an experimental weapon that could very well lead to the complete destruction of Sidonia.

In order to pursue her dream of bringing positive changes to Japan, Mitsumi Iwakura leaves her countryside town to attend a prestigious high school in the hustle and bustle of Tokyo. As she has already mapped a clear life plan, she has absolute confidence that there will be zero mishaps from then onwards. Despite her ambitious promise, the country girl ends up running late on the first day when she gets lost on her way to school. Fortunately, she meets a fellow first-year student, Sousuke Shima, who is in the same situation and offers to go with her. They eventually make it to school, but the misfortunes do not end there, as Mitsumi leaves an unfavorable first impression in front of her classmates. Nevertheless, the class soon takes notice of her friendship with Sousuke despite their opposing personalities. Only time will tell whether Mitsumi will be able to forge fruitful relationships with her classmates, and she will certainly not be alone.

Saku Ooyagi returns to his hometown after seven years and is soon reacquainted with his childhood friend, Mihoshi Akeno. The reunion is far from merry since the last memory they have of each other is of her falling off a tree and him saving her. In any case, Mihoshi is determined to improve their relationship and forces Saku to join the astronomy club she founded.