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Objective Deep neck infection (DNI) associated with descending necrotizing mediastinitis (DNM) is a highly lethal condition. This retrospective review was performed to share our experience performing multidisciplinary management of DNI associated with DNM during a 7-year period. Methods We reviewed 16 patients who had been surgically treated for DNM at Peking Union Medical College Hospital from April 2010 to July 2017. The clinical outcomes were analysed to determine the most appropriate therapeutic strategy. Results Five women and 11 men were included in this study. Their mean age was 54.9 ± 14.3 years. DNM-associated infections most commonly occurred secondary to odontogenic infections (n = 10). Thirteen patients required tracheotomy because of tracheal compression. All patients underwent unilateral or bilateral cervicotomy. Six patients with DNM localized in the upper mediastinal space underwent transcervical mediastinal drainage, while 10 patients with DNM extending to the lower mediastinum were treated by cervicotomy and video-assisted thoracoscopic surgery. Three patients died of multiple organ failure. Conclusion Multidisciplinary treatment can achieve favourable outcomes in >80% of patients with DNM. Early diagnosis, proper airway management, and adequate surgical drainage are crucial for reducing mortality in patients with DNM, and minimally invasive procedures also play an important role.