Objective Necrotizing soft-tissue infection (NSTI) in the head and neck area may develop from odontogenic infections. The aim of this study was to characterize patients with NSTI in the head and neck with odontogenic origin in a well-defined prospectively collected cohort. Material and methods Patients with NSTI in the head and neck, hospitalized between 2013 and 2017 at Copenhagen University Hospital and registered in the Scandinavian INFECT database were included. Medical records of identified patients and from the INFECT database were screened for a defined set of data including the primary focus of infection, comorbidities, predisposing factors, clinical and radiographic diagnostics, course of treatment, and treatment outcome. Results Thirty-five patients with NSTI in the head and neck area were included in the study. A total of 54% had odontogenic origin, primarily from mandibular molars, and 94% had radiographic signs of infectious oral conditions. Overall, comorbidities were reported in 51% with cardiovascular disease being the most prevalent. In 20%, no comorbidities or predisposing conditions could be identified. The overall 30-day mortality rate was 9%. Conclusions More than half of NSTI cases in the head and neck region had an odontogenic origin, and special attention should be paid to infections related to mandibular molars.