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Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the disease it causes, coronavirus disease 2019 (COVID-19), has spread rapidly across the globe resulting in more than 7,000,000 cases and 400,000 deaths worldwide, of which 52,991 cases and 1162 deaths have occurred in South Africa. Objective: To describe the clinical characteristics of the first 100 patients with COVID-19 admitted to a tertiary hospital in Johannesburg, South Africa. Methods: We conducted a single-centre retrospective review of the first 100 patients with reverse transcriptase polymerase chain reaction-confirmed COVID-19 infection admitted to a tertiary academic hospital in Johannesburg, South Africa. Results: The 100 patients were predominantly male (53%), of black ethnicity (79%) and had a median age of 42 years. The most common comorbidities were hypertension (31%), diabetes mellitus (18%) and 47% of the patients had an endomorphic phenotype. Eleven per cent (11%) of our patients were HIV positive. During hospitalisation, 14 patients (14%) required admission to the intensive care unit (ICU). For those patients with an outcome available, the overall mortality rate was 10% (n = 6), and 57% (n = 4/7) for those admitted to the ICU. Mean length of stay for those who had died or had been discharged was 6.8 days. Conclusion: This case series describes clinical characteristics in the first 100 patients with confirmed COVID-19 admitted to a large centre in Johannesburg, South Africa. Our findings are concordant with universally reported data; however, more data is needed on COVID-19 in the South African setting, specifically related to tuberculosis and HIV.