In recent years, both the number of patients with breast cancer and those with associated brain metastases (BMs) have increased. Human epidermal growth factor receptor 2 (HER2)-positive breast cancer has a high BM frequency. The prognosis of BM from breast cancer is poor, and establishing effective treatment for this disease is essential. We report a HER2-positive patient with multiple BM and right-eye blindness due to pituitary metastasis. She responded promptly to trastuzumab deruxtecan (T-DXd) in the 5th line of treatment, which shrunk the tumors and restored vision. Although the Graded Prognostic Assessment (GPA) predicted survival of 13 months, the patient recovered well after treatment and continued T-DXd use with no progression, including vision loss at 22 months after treatment initiation. This case demonstrates the successful action of T-DXd in the face of multiple BM and poorly predicted outcomes.