"Q.E.D." is a detective manga series that centers around Sou Touma, a brilliant high school student with a genius-level intellect, and his classmate Kana Mizuhara, a spirited and curious girl. The narrative unfolds through a series of standalone cases, each presenting a unique mystery that Touma and Mizuhara work together to solve. Touma, who graduated from MIT at a young age, approaches problems with a logical and analytical mindset, often drawing on his vast knowledge of mathematics, science, and history. Mizuhara, while not as academically gifted, provides a grounded perspective and emotional insight, balancing Touma's rationality with her intuition and determination.

The mysteries in "Q.E.D." range from seemingly simple puzzles to complex criminal investigations, often involving themes of human psychology, societal issues, and historical events. Touma's deductive reasoning and ability to connect seemingly unrelated clues drive the solutions, while Mizuhara's persistence and empathy help uncover the human elements behind each case. The series frequently explores the motivations and moral dilemmas of the individuals involved, adding depth to the mysteries.

Supporting characters include Touma's older sister, Rika Touma, a lawyer who occasionally assists with legal aspects of the cases, and various recurring figures who appear in specific story arcs. The manga maintains a balance between intellectual challenges and character-driven storytelling, with Touma and Mizuhara's evolving dynamic serving as a consistent thread throughout the series. The narrative structure emphasizes problem-solving and critical thinking, often presenting readers with the opportunity to piece together clues alongside the protagonists. The series is notable for its meticulous attention to detail and its integration of real-world knowledge into its fictional mysteries.