The United Nations Sustainable Development Goal target 6.1 calls for universal and equitable access to safe and affordable drinking water. Worldwide, about 2.2 billion people live without access to safe water, and millions of people suffer from waterborne pathogens each year, representing the most pressing situation in developing countries. The aim of this study was to investigate the drinking water quality dynamics across an endemic cholera sub-Saharan country (Guinea-Bissau), and understand its implications for public health. Microbiological and physical–chemical quality parameters of 252 major water sources spread all over the country were seasonally surveyed. These comprised hand-dug shallow wells and boreholes, fitted with a bucket or a pump to retrieve water. The results showed that the majority of water sources available to the population were grossly polluted with faecal material (80%), being unsuitable for consumption, with significantly (p < 0.05) higher levels during the wet season. Hand-dug wells revealed the highest contamination levels. The chemical contamination was less relevant, although 83% of the water sources were acidic (pH < 6.5). This study highlights the potential health risk associated with the lack of potable drinking water, reinforcing the evidence for water monitoring, and the need to improve WASH (water, sanitation, and hygiene) infrastructure and water management in West African countries. In addition, the authors suggest easy-to-implement interventions that can have a dramatic impact in the water quality, assisting to reduce the associated waterborne diseases rise.