Descending necrotizing mediastinitis (DNM) is a devastating complication of cervical or odontogenic infections that can spread downward to the mediastinum through anatomic spaces. We report the case of an intravenous drug user who presented with rapidly propagating acute pericarditis and DNM as the early presentations of pyomyositis of the sternocleidomastoid muscle and deep neck infection. The patient was successfully treated with antibiotics and surgical drainage. Clinicians should be aware that pathogens injected into the carotid sheath may spread to the mediastinum and/or pericardium and manifest as DNM and/or pericarditis prior to infectious signs and symptoms at the site of injection.