As anthropogenic pressures continue to impact the environment, human health is expected to be subsequently affected. This dataset provides a comprehensive view of the trends and burden of infectious diseases, along with environmental metrics, across the Amazon biome between 2000 and 2019. The dataset includes health indicators for respiratory, cardiovascular, and major zoonotic and vector-borne diseases (Chagas disease, hantavirus, cutaneous leishmaniasis, visceral Leishmaniasis, rickettsial diseases, and malaria), compiled as annual case counts at the municipal level. The innovation of this dataset lies in its unprecedented assembly of data for this transboundary biome—much of it requiring ground-level collection beyond available in online repositories. By integrating health and environmental indicators, this dataset offers a unique resource for analyzing the complex relationships between environmental transformations and health outcomes. It supports future research informing evidence-based public health strategies, and conservation efforts to address the interconnected socio-environmental challenges of this cornestone of planetary health, home to more than 30 million people.