The study of the microbiome has significantly contributed to our understanding of complex diseases including cancer, with a profound influence of the microbiota on clinical prognosis and the efficacy of cancer treatments. Oesophageal cancer is positioned amongst the most aggressive malignant diseases, resulting from a complex interaction between anthropometric, genetic, immune response, and environmental factors. Oesophageal squamous cell carcinoma (OSCC) is the most common type of oesophageal cancer and is a serious burden in Eastern Africa, in the area known as the African oesophageal cancer corridor (AOCC). OSCC is often diagnosed at a late stage, with patients already suffering from severe malnutrition and dehydration due to swallowing difficulties, leading to high mortality rates. So far, aetiological factors have been individually analysed with an inappropriate contextualisation. The upper digestive tract microbiome has been proposed to contribute to the onset and progression of OSCC but with limited understanding of the mechanisms behind this interaction. Data on African populations are limited, and the aetiology of AOCC is still poorly understood. This review discusses the current knowledge of the aetiology of OSCC in Africa, with special focus on the probable influence of the upper digestive tract microbiota.