Background: There have been insufficient data for African patients with COVID-19 who are critically ill. The African COVID-19 Critical Care Outcomes Study (ACCCOS) aimed to determine which resources, comorbidities, and critical care interventions are associated with mortality in this patient population. Methods: The ACCCOS study was a multicentre, prospective, observational cohort study in adults (aged 18 years or older) with suspected or confirmed COVID-19 infection who were referred to intensive care or high-care units in 64 hospitals in ten African countries (ie, Egypt, Ethiopia, Ghana, Kenya, Libya, Malawi, Mozambique, Niger, Nigeria, and South Africa). The primary outcome was in-hospital mortality censored at 30 days. We studied the factors (ie, human and facility resources, patient comorbidities, and critical care interventions) that were associated with mortality in these adult patients. This study is registered on ClinicalTrials.gov, NCT04367207. Findings: From May to December, 2020, 6779 patients were referred to critical care. Of these, 3752 (55·3%) patients were admitted and 3140 (83·7%) patients from 64 hospitals in ten countries participated (mean age 55·6 years; 1890 [60·6%] of 3118 participants were male). The hospitals had a median of two intensivists (IQR 1–4) and pulse oximetry was available to all patients in 49 (86%) of 57 sites. In-hospital mortality within 30 days of admission was 48·2% (95% CI 46·4–50·0; 1483 of 3077 patients). Factors that were independently associated with mortality were increasing age per year (odds ratio 1·03; 1·02–1·04); HIV/AIDS (1·91; 1·31–2·79); diabetes (1·25; 1·01–1·56); chronic liver disease (3·48; 1·48–8·18); chronic kidney disease (1·89; 1·28–2·78); delay in admission due to a shortage of resources (2·14; 1·42–3·22); quick sequential organ failure assessment score at admission (for one factor [1·44; 1·01–2·04], for two factors [2·0; 1·33–2·99], and for three factors [3·66, 2·12–6·33]); respiratory support (high flow oxygenation [2·72; 1·46–5·08]; continuous positive airway pressure [3·93; 2·13–7·26]; invasive mechanical ventilation [15·27; 8·51–27·37]); cardiorespiratory arrest within 24 h of admission (4·43; 2·25–8·73); and vasopressor requirements (3·67; 2·77–4·86). Steroid therapy was associated with survival (0·55; 0·37–0·81). There was no difference in outcome associated with female sex (0·86; 0·69–1·06). Interpretation: Mortality in critically ill patients with COVID-19 is higher in African countries than reported from studies done in Asia, Europe, North America, and South America. Increased mortality was associated with insufficient critical care resources, as well as the comorbidities of HIV/AIDS, diabetes, chronic liver disease, and kidney disease, and severity of organ dysfunction at admission. Funding: The ACCCOS was partially supported by a grant from the Critical Care Society of Southern Africa.