Hypothalamic obesity (HO) is a severe complication of suprasellar tumors characterized by hyperphagia, rapid weight gain, and resistance to lifestyle interventions. We describe a case of a woman diagnosed with suprasellar germinoma at 16 years of age who was treated with chemotherapy and radiotherapy. Subsequently, she experienced progressive weight gain, increasing from 57 kg to a peak of 138 kg by age 37 years, and developed type 2 diabetes mellitus at age 28 years. At age 38 years, she presented with polydipsia, polyuria, and fatigue, and was admitted for the management of hyperglycemia with class III obesity (123.5 kg; body mass index [BMI], 51.4 kg/m). Intensive insulin therapy (up to 100 units/day) resolved glucotoxicity. After initiation of semaglutide (titrated from 0.25 to 0.5 mg/week), appetite markedly decreased, and subsequent weight loss was achieved. Three months after discharge, her weight decreased from 131 kg to 112.1 kg, representing an approximate 14% reduction, accompanied by optimized glycemic control. Body composition analysis revealed that weight loss was primarily due to fat mass reduction with relative preservation of muscle mass. This case demonstrates the potential efficacy of semaglutide in patients with HO and type 2 diabetes mellitus after suprasellar germinoma treatment.