"Tying the Knot With an Amagami Sister" centers around Uryu Kamihate, a young man who, after losing his parents, is taken in by the Amagami family, a lineage of shrine priests. The Amagami household consists of three sisters—Asahi, Yae, and Miko—each with distinct personalities and roles within the family shrine. Uryu’s arrival disrupts their routine, as he is unexpectedly chosen by the family’s divine protector, a fox spirit, to become the next shrine priest. This decision creates tension, as the sisters had assumed one of them would inherit the role.

Asahi, the eldest, is responsible and pragmatic, often acting as the family’s anchor. Yae, the middle sister, is cheerful and outgoing, balancing her duties with a playful demeanor. Miko, the youngest, is reserved and studious, deeply devoted to the shrine’s traditions. Uryu, initially an outsider, struggles to adapt to his new responsibilities and the sisters’ contrasting expectations. The narrative explores his efforts to prove himself worthy of the role while navigating the complexities of living with the Amagami sisters.

The story intertwines supernatural elements with slice-of-life moments, as Uryu learns about the shrine’s rituals and the fox spirit’s influence. The sisters’ relationships with Uryu evolve, shifting from skepticism to mutual respect and camaraderie. Romantic undertones emerge, particularly as Uryu grows closer to each sister, though the focus remains on their collective journey to preserve the shrine’s legacy. The series balances humor, emotional depth, and cultural exploration, offering a blend of lighthearted interactions and moments of introspection. Themes of family, tradition, and personal growth are central, as the characters confront their insecurities and aspirations while upholding the shrine’s sacred duties.