The Neuroi, an enemy of mankind, suddenly appeared mainly in Europe in the 1930s. Only girls with special magical powers called Witches could confront the Neuroi who were difficult to destroy with ordinary weapons. In 1944, the Neuroi nest above the republic of Gallia was eradicated, and safety of western Europe has been ensured. The allied forces earnestly began planning for an oppositional operation towards central and eastern Europe. An order to scramble is given to the 502nd Joint Fighter Wing "Brave Witches" whose base is in Peterburg within the Orussian Empire.
Ash is a student at Ansalivan Dragon Academy, attended by children who have formed contracts with dragons. He possesses the "star mark," the sign of a contract, but since his partner hasn't been born yet, he seems insignificant. The awakening of the dragon he's raising inside his body is triggered by an incident, and it emerges in the form of a young girl.
A gate appears in Tokyo's Ginza district sometime in the 21st century. From the gate pours out monsters, knights from middle-age Europe, and other fantasy-like beings, and they kill many of the citizens of Tokyo. This event is known as the Ginza Incident. The government sends a small group of soldiers from the Japanese Self-Defense Forces to the alternate world beyond the gate. Led by otaku soldier Yōji, they find that the villages in the world are being attacked by a dragon. An elf girl who is a survivor from the dragon's rampage joins the group in their travels across the dangerous new world.
In 1939, the imperialist nation of Germania launched a sudden invasion of its neighboring countries. This conflagration engulfed all of Europe in one fell swoop, and the era was dragged into the maelstrom of war. Then in 1940, Germania set its sights on Elystadt, a tiny principality blessed with breathtaking greenery and water in the Alps. Izetta is a descendant of a clan of witches who had passed down mysterious powers for generations. Since she was little, she and her grandmother lived their lives on the road, traveling between European countries in order to hide these powers. Fiine is the sole daughter in line to succeed Rudolph III, the ruler of the Principality of Elystadt. Since her father has been stricken by illness, she has been busy preparing for Germania's invasion in his stead.
Tokiha Mai and her sickly younger brother, Takumi, have received a scholarship to attend the prestigious Fuuka Academy. On the way, the ferry they are travelling on becomes the site of a destructive battle between two girls wielding apparently supernatural powers. This is only the beginning of their troubles, as Mai learns that she herself possesses these powers - the powers of a HiME.
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.
In Oshima the happy, carefree 14-year-old Akane Isshiki lived a poor but well-loved life together with her reliable little sister, Momo, who does all the housework, and her grandfather, Kenjirō, a genius inventor who only created useless devices. When the weather is clear, they can see the artificial island, Blue Island, across the sea. In the center of that island rises the revolutionary Manifestation Engine, a discovery that solved the world's energy problems, and leads to some major problems.