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The Amazon Delta and Estuary (ADE) is a region of continental and global ecological importance. Controversy, many of the basic infrastructure and services essential for quality of life and sustainable development of this delta are absent. Using a conceptual model to define socio-economic vulnerability in the urban ADE, a thorough assessment of indicators including sanitation services, housing conditions, household income, population, flood risk and unplanned settlements was conducted in 41 cities at the census sector scale (n = 2938). A multi criterion index was applied to classify urban vulnerability from three dimensions: flood exposure, socio-economic sensitivity and infrastructure. This is the first study to examine urban vulnerability within and between urban areas of the ADE. Results indicated that most of the urban sectors of the ADE are exposed to potential risks due to a combination of flood hazards, poverty and basic structural deficiencies such as insufficient drinking water or inadequate waste water collection, with several sectors being afflicted by similar problems. The assessment of vulnerability indicates that 60-90 % of the urban population live in conditions of moderate to high degree of vulnerability. The ADE cities presented a pattern where vulnerability increases from city center to their newly developed urban areas. Inadequate planning coupled with rapid urbanization has contributed to the development of unplanned settlements in almost half of the urban sectors of the ADE. Combined, these factors contribute to widespread socio-economic vulnerability along the urban spaces of the ADE, increasing exposure to health risks and more frequent seasonal and stochastic events such as storm surges and high flooding levels.