Thirty years ago a strange phenomenon called a "spacequake" devastated the center of Eurasia, claiming the lives of at least 150 million people. Since then, smaller spacequakes plague the world on an irregular basis. Shido Itsuka, a seemingly ordinary high schooler comes across a mysterious girl at the ground zero of a spacequake and learns from his sister Kotori she is one of the "Spirits" who are the real cause of the spacequakes that occur when they manifest themselves in the world. He also learns that Kotori is the commander of the airship Fraxinus, crewed by the organization Ratatoskr, and is recruited to make use of his mysterious ability to seal the Spirits' powers thus stopping them from being a threat to mankind. However, there is a catch: to seal a Spirit's power, he must make her fall in love with him and kiss him.
Madoka is the lone member of her school's Jersey Club. She is one day recruited by a mysterious girl named Lan to pilot the robot "Vox" and protect her city from space invaders. They are joined by a third girl, Muginami, who has a different goal than Ran. Meanwhile, they still don't know their enemies' true goal, or what "Rinne" might be.
The year is 1939 - it was then that the Neuroi appeared. Nobody knows where they came from or what their ultimate agenda is, but the fact remains that their attacks drove people out of their towns and cities. In order to take arms against them, humanity develops a new anti-Neuroi weapon called the "Striker Unit." Using the power of magic to fight against the monsters, this new device enhances and amplifies the power of female magic-wielders. To use this device, young witches from all over the world have been brought together to form an elite task force unit called the 501st Joint Fighter Wing, commonly known as the "Strike Witches."
After discovering that Neuroi are capable of communication with humans and making peace with the nest above Gallia, the Witches squads are now on a mission to re-establish communication when the Neuroi completely vanish after a sudden attack. It is then that they discover a new massive nest that just appeared covering almost all of Europe. Ruthless and without mercy it annihilates allied forces along with many Witches. Word of the attack reaches Fuso and a support battalion is deployed to rescue the survivors. Among the rescue team is the former Striker captain Sakamoto Mio and the now civilian Miyafuji Yoshika who wants to save her dear friends.