Abstract Background Severe acute malnutrition (SAM) is a major public health concern responsible for paediatric hospitalizations and more than one-third of deaths across the world. In 2013, SAM caused ≥20% of deaths in severely malnourished infants in Douala, the economic capital of Cameroon. There is little data on SAM in economically, sanitary and socially disadvantaged Cameroonian regions including the North region. Objectives To determine the prevalence and potential predictors of mortality among children with SAM in a reference health facility in Garoua, North region, Cameroon. Methods A cross-sectional analytical study was conducted from November 2021 to May 2022 at the paediatric ward of Garoua Regional hospital. Data collected on sociodemographic, clinical and therapeutic characteristics in this study were questionnaire based. Results A total of 6769 children were admitted for hospitalization during the study period, among them 701 SAM cases, giving a hospital prevalence of 10.4%. Of the 347 children included, 51% of the study population were males and 87.6% were children aged 6–23 months. Seven predictors of mortality were identified: orphan status [adjusted odds ratios (AOR) = 8.70, p = 0.021], vomiting (AOR = 3.40, p < 0.0001), marasmus–kwashiorkor (AOR = 7.30, p = 0.005), lack of appetite (AOR = 56.10, p < 0.0001), cutaneous lesions (AOR = 5.50, p = 0.014), lethargy (AOR = 4.50, p = 0.001) and nasogastric rehydration (AOR = 6.50, p = 0.004). Conclusion Practitioners in the northern region of Cameroon should address these locally identified mortality factors to intervene with, and hopefully prevent and adequately manage malnutrition and SAM in this and similar contexts.