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The Brazilian Amazon is one of the areas on the planet with the fastest changes in forest cover due to deforestation associated with agricultural expansion and infrastructure development. These drivers of change, directly and indirectly, affect the water ecosystem. In this study, we present a long-term spatiotemporal analysis of surface water annual change and address potential connections with deforestation, infrastructure expansion and climate change in this region. To do that, we used the Landsat Data Archive (LDA), and Earth Engine cloud computing platform, to map and analyze annual water changes between 1985 and 2017. We detected and estimated the extent of surface water using a novel sub-pixel classifier based on spectral mixture analysis, followed by a post-classification segmentation approach to isolate and classify surface water in natural and anthropic water bodies. Furthermore, we combined these results with deforestation and infrastructure development maps of roads, hydroelectric dams to quantify surface water changes linked with them. Our results showed that deforestation dramatically disrupts small streams, new hydroelectric dams inundated landmass after 2010 and that there is an overall trend of reducing surface water in the Amazon Biome and watershed scales, suggesting a potential connection to more recent extreme droughts in the 2010s.