"Polyphonica" is set in a world where music holds magical properties, capable of influencing the environment and summoning spirits known as Spirits of Music. The story unfolds in the city of Marugensho, where the Academy of Spirits trains individuals called Dantists, who specialize in using music to communicate with and control these spirits. The protagonist, Phoron Tatara, is a young Dantist student with a mysterious past and a unique connection to the Spirits of Music. His abilities are tied to a powerful and enigmatic spirit named Corticarte Apa Lagranges, often referred to as Corti, who serves as his partner.

The narrative explores Phoron's journey as he navigates the complexities of his role as a Dantist, balancing his studies with the responsibilities of managing his bond with Corti. Their relationship is central to the plot, as Corti's immense power and unpredictable nature often lead to conflicts and challenges. Together, they undertake various missions, ranging from resolving disputes involving rogue spirits to uncovering the deeper mysteries of the world's musical magic.

Supporting characters include Eufinley Tsuge, a fellow Dantist and Phoron's childhood friend, who provides emotional grounding and a contrasting perspective on the use of musical magic. The series also introduces other Dantists and spirits, each with their own motivations and backstories, contributing to the rich tapestry of the world. As the story progresses, Phoron and Corti uncover secrets about the origins of Spirits of Music and the true nature of their connection, leading to revelations that challenge their understanding of their roles and the world around them.

The plot intertwines episodic adventures with an overarching narrative, blending action, mystery, and elements of fantasy. Themes of trust, identity, and the power of music are explored through the interactions between humans and spirits, as well as the ethical dilemmas faced by Dantists in their use of magical music. The series maintains a balance between character-driven moments and larger plot developments, creating a cohesive and engaging storyline.