Atypical hemolytic uremic syndrome (aHUS) is characterized by thrombotic microangiopathy secondary to uncontrolled activation of the complement system. Extra-renal manifestations of aHUS affect the prognosis of this condition; therefore, optimal management of extra-renal manifestations of aHUS is important. A 3-year-old girl admitted with hematuria, proteinuria, and generalized edema was diagnosed with aHUS. We report a pediatric case of life-threatening extra-renal manifestations of aHUS, including gastrointestinal bleeding, refractory hypertension, pulmonary edema, and reversible cerebral atrophy in a patient who was successfully treated with multidisciplinary treatment. In addition to plasma exchange and eculizumab combination therapy, we administered renin-angiotensin system inhibitors for refractory hypertension and octreotide acetate for body fluid management in ischemic enteritis. Notably, multi-organ involvement in patients with extra-renal manifestations of aHUS can result in serious complications in the absence of appropriate treatment; therefore, systemic management with multidisciplinary treatment is important for improved prognosis.