Setsuna is the younger fraternal twin daughter of Sesshōmaru and Rin, born during a lunar eclipse in Kaede's village. Sesshōmaru took the newborn twins to a forest for protection from Zero, who sought to eliminate them due to a prophecy that half-demons would slay Kirinmaru. Jaken placed a protective barrier around them. At age four, during a forest fire orchestrated by Homura under Zero's orders, Setsuna was separated from her sister Towa, who vanished through a time portal to the modern era. Jaken returned after the fire and placed a chrysalis of a Dream Butterfly on the crying Setsuna to alleviate the Silver-Scale Curse affecting Rin, severing Setsuna's ability to dream and erasing her childhood memories. She was taken to the Hanyō Hidden Village, cared for by Shiori for six years, before briefly returning to her birth village.

During an attack on the hidden village by Gaga Gozen in a total solar eclipse, Setsuna's demon blood awakened while she was restrained. She broke free in a rampage, tearing Gaga Gozen apart and attacking Miroku, who subdued her with Shiori's help. Miroku applied a seal to prevent future rampages, suppressing her visible demon traits like claws, fangs, and markings. Shiori then convinced Setsuna to return to Kaede's village, where she trained under Kohaku as a demon slayer.

Ten years after the separation, Setsuna reunited with Towa and met her half-cousin Moroha. She displayed a calm, unflappable personality reminiscent of her father, often appearing aloof and cynical. She expressed resentment toward her half-demon status and indifference toward Sesshōmaru, whom she deemed unworthy of being called her father due to his absence. She rejected Towa's attempts at closeness, irritated by her sister's modern-era soft-heartedness. Setsuna believed in using lethal force against enemies for survival, though she avoided killing demons when possible during patrols. She respected Kohaku, Hisui, and Kaede, and developed a familial bond with the Higurashi family after staying with them.

During their travels, Setsuna and her companions faced adversaries like members of the Shikyō. Her lack of dreams made her immune to dream-based attacks, seen when she destroyed Yotsume. In battles, she often recited prayers learned from Miroku to absolve fallen foes. Kirinmaru seemingly killed her, but Towa revived her using the broken Tenseiga, reforged into Yukari no Tachikiri. The restoration of her dreams and memories via the Dream Butterfly softened her demeanor. She tearfully called Towa "sis" during a critical battle, embraced her, and acknowledged Moroha as a friend, later showing visible emotion when Moroha reunited with her parents.

Physically, Setsuna has fair skin, long black hair with two red streaks tied in a high ponytail, and purple eyes. Under Miroku's seal, she lacked visible demon traits, passing as human. When unsealed, her nails become claws, her canines sharpen, magenta markings similar to Sesshōmaru's appear, and her ears become pointed. In a full demon state induced by Zero, she gains a violet crescent moon forehead marking, orchid butterfly wings, red sclera, and a green aura, retaining a dark crimson arm marking afterward. She wears a navy kimono-like jumpsuit with deep violet armor. She cherished a violin given by Moe Higurashi. Her fighting style combines demon slayer techniques with inherited demonic abilities, evolving to include strategic uses of her unsealed power and the Yukari no Tachikiri, which can sever threads of fate.