Necrotizing soft tissue infection (NSTI) is a rapidly progressive infection that typically starts in the dermis and epidermis and spreads along soft tissue planes, penetrating subdermal layers and can lead to massive tissue necrosis resulting in severe morbidity and mortality. The aim of this case series was to describe the epidemiology and burden of NSTI's at a District Hospital servicing a South African urban settlement. This retrospective case series was performed at a single centre. Consecutive patients were identified following a clinical diagnosis for NSTI. Further laboratory pre-operative work up was standardized including: use of validated Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC scores) and Human Immunodeficiency Virus (HIV) status. All patients who underwent surgical debridement were captured on the Theatre Database ( 28 patients (14 male, 14 female) presented with NSTI over a 3 year period (2021–2023). The mean age was 39.5 years. The most common organisms cultured were Streptococcus pyogenes (10 patients), Staphylococcus aureus (9 patients), Bacillus cereus (3 patients). This retrospective case series is an important study because it demonstrates some of the highest incidence of NSTI globally; however, the cause of this is yet to be determined. Our results show that having a high clinical index of suspicion; using the LRINEC score to assess severity and using a standardized antibiotic and peri-operative protocol with early soft tissue cover that NSTI's can be managed effectively with a reduction in patient morbidity and overall length of hospital stay.