Amazonian ecosystems are major biodiversity hotspots and carbon sinks that may lose species to extinction and become carbon sources due to extreme dry or warm conditions. We investigated the seasonal patterns of high-resolution solar-induced chlorophyll fluorescence (SIF) measured by the satellite Orbiting Carbon Observatory-2 (OCO-2) across the Amazonian ecoregions to assess the areás phenology and extreme drought vulnerability. SIF is an indicator of the photosynthetic activity of chlorophyll molecules and is assumed to be directly related to gross primary production (GPP). We analyzed SIF variability in the Amazon basin during the period between September 2014 and December 2018. In particular, we focused on the SIF drought response under the extreme drought period during the strong El Niño in 2015–2016, as well as the 6-month drought peak period. During the drought´s peak months, the SIF decreased and increased with different intensities across the ecoregions of the Amazonian moist broadleaf forest (MBF) biome. Under a high temperature, a high vapor pressure deficit, and extreme drought conditions, the SIF presented differences from −31.1% to +17.6%. Such chlorophyll activity variations have been observed in plant-level measurements of active fluorescence in plants undergoing physiological responses to water or heat stress. Thus, it is plausible that the SIF variations in the ecoregions’ ecosystems occurred as a result of water and heat stress, and arguably because of drought-driven vegetation mortality and collateral effects in their species composition and community structures. The SIF responses to drought at the ecoregional scale indicate that there are different levels of resilience to drought across MBF ecosystems that the currently used climate- and biome-region scales do not capture. Finally, we identified monthly SIF values of 32 ecoregions, including non-MBF biomes, which may give the first insights into the photosynthetic activity dynamics of Amazonian ecoregions.