The resilience of the Amazon rainforest to climate and land-use change is crucial for biodiversity, regional climate, and the global carbon cycle. Deforestation and climate change, via increasing dry-season length and drought frequency, may already have pushed the Amazon close to a critical threshold of rainforest dieback. Here, we quantify changes in Amazon resilience by applying established indicators (for example, measuring lag-1 autocorrelation) to remotely sensed vegetation data with a focus on vegetation optical depth (1991–2016). We find that more than three-quarters of the Amazon rainforest has been losing resilience since the early 2000s, consistent with the approach to a critical transition. Resilience is being lost faster in regions with less rainfall and in parts of the rainforest that are closer to human activity. We provide direct empirical evidence that the Amazon rainforest is losing resilience, risking dieback with profound implications for biodiversity, carbon storage, and climate change on a global scale.