Descending necrotizing mediastinitis (DNM) is a rare form of mediastinal infection. Most cases are associated with esophageal rupture. DNM after a trigger point injection in the upper trapezius has not been described previously. We present a case of DNM after a trigger point injection in the upper trapezius. A 70-year-old man visited the emergency department with chest discomfort and fever after a trigger point injection in the left upper trapezius. Chest computed tomography showed evidence of DNM, and antibiotic therapy was immediately administered intravenously. Because of the risk of sudden death, poor prognosis due to underlying disease, and his age, he declined surgical treatment and died of septic shock. Although trigger point injections are generally considered safe, caution should be used in patients with an underlying disease or in the elderly. Early diagnosis, broad-spectrum antibiotics, and aggressive surgical management are essential to improve the prognosis.