Amazonian Indigenous Lands (ILs) are human-environment systems facing a multitude of environmental threats. Yet, the resulting vulnerability of these systems are to date unknown. We adopt the theoretical vulnerability framework of the IPCC to assess the environmental vulnerability of Brazilian Amazon ILs for two periods (2001–2010 and 2011–2019) and overall (2001–2019). Vulnerability is deemed a function of exposure (EX), sensitivity (SE) and adaptive capacity (AC) of a system to threats. Sensitivity (threats within IL) and exposure (threats in IL's buffer zones) indicators are changes in forest cover, economic activities, and road access, quantified using data of deforestation, forest degradation, land-use, fire, roads and mining. Adaptive capacity indicators represent Indigenous self-organization, education and access to knowledge, land ownership, external incomes, and institutional arrangement. We find a concentration of ILs with high vulnerability in the Arc of Deforestation and South, and advancing in Pará and Roraima states. A strong relationship (Spearman r = 0.79) between EX and SE indicates the strong pressure exerted by external processes. An increase in EX (73.9% of the ILs) and in SE (64.8% of the ILs) in 2011–2019 compared to 2001–2010 signals a worrying rise in vulnerability recently. We advise the adoption of policies by the State, such as combating illegal activities, and strengthening National Policy for Environmental and Territorial Management of ILs. Herein, our vulnerability quantification can prioritize help to certain ILs, and the understanding of the contribution of the underlying dimensions can direct these policies, possibly according to the vulnerability profile of each IL.