Sakuta Azusagawa endured profound family trauma after his sister Kaede suffered cyberbullying-induced spontaneous injuries, dissociative identity disorder, and memory loss. This catalyzed his Adolescence Syndrome, marked by three claw-like chest scars that reopen during emotional distress. His subsequent hospitalization spawned false rumors of violence—the "Hospitalization Incident"—causing social isolation. During this period, Shoko Makinohara’s counsel at Shichirigahama Beach to "live kindly" shaped his philosophy, leading him to discard his phone in solidarity with Kaede.

Sakuta maintains a deadpan, stoic exterior, delivering blunt or lewd remarks without emotional shifts. Despite social detachment, he displays selflessness and compassion toward fellow Adolescence Syndrome sufferers, guided by the belief that acceptance from one person justifies enduring universal scorn. He employs analytical problem-solving and defies social norms while privately grappling with rumor-induced pain.

His relationship with Mai Sakurajima ignited when he alone witnessed her invisibility-like Adolescence Syndrome episode. Supporting her through the ordeal culminated in a public love declaration that restored her visibility. Their committed partnership navigates Mai’s acting career pressures and her jealousy over his interactions with others, though he remains steadfastly faithful.

Sakuta protects Kaede in a separate apartment, encouraging her social reintegration despite setbacks like memory fluctuations and collapses. He forged key bonds with other syndrome-affected individuals: Rio Futaba, whose scientific insights aided his understanding; Tomoe Koga, assisted through a fabricated-dating scheme and time-loop crisis; and Nodoka Toyohama, Mai’s half-sister, whom he helped overcome identity and self-esteem struggles. His connection to Shoko Makinohara spanned multiple timelines, including a pivotal convergence of her adolescent and adult selves requiring temporal intervention to avert tragedy.

Post-high school, Sakuta studied statistical science at Yokohama City University alongside Mai. He mentored students like Sara Himeji at a cram school job while forming new ties with Uzuki Hirokawa, Ikumi Akagi (a middle school classmate), and Miori Mitou. He sustained friendships with Rio and Tomoe and encountered another syndrome case involving Touko Kirishima, a miniskirt Santa figure perceptible only to him who claimed to "gift" the affliction.