Filled with an overwhelming sense of wonder for the world around her, Mari Tamaki has always dreamt of what lies beyond the reaches of the universe. However, despite harboring such large aspirations on the inside, her fear of the unknown and anxiety over her own possible limitations have always held her back from chasing them. But now, in her second year of high school, Mari is more determined than ever to not let any more of her youth go to waste. Still, her fear continues to prevent her from taking that ambitious step forward—that is, until she has a chance encounter with a girl who has grand dreams of her own. Spurred by her mother's disappearance, Shirase Kobuchizawa has been working hard to fund her trip to Antarctica. Despite facing doubt and ridicule from virtually everyone, Shirase is determined to embark on this expedition to search for her mother in a place further than the universe itself. Inspired by Shirase's resolve, Mari jumps at the chance to join her. Soon, their efforts attract the attention of the bubbly Hinata Miyake, who is eager to stand out, and Yuzuki Shiraishi, a polite girl from a high class background. Together, the four spirited girls set sail toward the frozen south, all in search of something great.

Preparations for a new offensive against the Neuroi—a mysterious race of alien invaders—are well underway. The objective is securing Berlin, the capital city of the Empire of Karlsland, which is necessary for wiping out the Neuroi threat from Europe. However, as the enemy is capable of adapting to the battlefield on a daily basis, the allied forces and the current state of Striker technology might not be enough to achieve a victory. Meanwhile, Yoshika Miyafuji, a Witch from Fuso, continues her medical studies in Lausanne. Having recovered from a recent incident that deprived her of magical power, she is eager to assist in the war effort. The call to arms soon arrives and the scattered witches of the 501st Joint Fighter Wing must be gathered once again for a final push against the enemy.

In a world plagued by magical dangers and threats, there exist special warriors—known as Inquisitors—who are tasked with non-violently preventing these threats and nefarious actions. The Anti-Magic Academy is a specialized school built to educate and train these Inquisitors, which splits its students into small squads in order to train them to work together. Among these talented squads is the 35th Test Platoon, also known as the Small Fry Platoon due to its low ranking and incompetent members. However, everything changes when Ouka Ootori, a powerful yet rebellious former Inquisitor, is forced into joining due to her tendency to break rules and committing a serious violation: the killing of a witch. Tempers flare upon her arrival, as she clashes with their clumsy captain Takeru Kusanagi and argues with the rest of the squad over her views on witches. This eclectic group has a long way to go if they wish to succeed and climb the ranks at the Anti-Magic Academy: they must first set aside their differences and come to work together as a team.

Kimihiko Kimizuka has found himself inadvertently entangled in various crimes more times than he can remember, referring to himself as a magnet for trouble. One day, as if it was nothing out of the ordinary, a group of unknown men kidnaps him, forcing him to board a flight—where he also encounters a hijacking. Amid the resulting chaos, however, Kimizuka meets a stunning silver-haired beauty, going by the codename Siesta, who then saves the day. Claiming to be a legendary detective, Siesta enlists Kimizuka to be her sidekick. Though Kimizuka refuses at first, with Siesta's insistence, he eventually joins her—marking the start of a grand adventure spanning the entire world, preventing multiple threats that could spell doom for humanity along the way. Unfortunately, after three years of their unpredictable yet enjoyable time together, Siesta abruptly passes away. Distraught, Kimizuka tries to leave all memories of her behind, but as he begins to meet more people, it seems that Siesta's influence will never truly die.