Transnational crime networks trafficking cocaine and gold are increasingly active in the Amazon. How international demand, trafficking, and impacts have changed, however, remain underexplored. We show that, annually, cocaine metabolite concentration in European sewage increased by 17% since 2011, while in the Brazilian Amazon cocaine seizures and gold royalties recently rose by ~50%, and forest loss in Peru since 2004 grew by 31% for every tenfold increase in coca cultivation with high recent losses (2019–2023). During this period, transnational networks of violent non-state actors (VNSAs) consolidated control over borders and triple borders, fostering environmental degradation. We also explore scenarios of relaxed cocaine prohibition and falling demand and find neither necessarily curbs conservation impacts because policy gradients between countries can increase crime or bifurcate markets into legal and illegal portions (as with gold), and traffickers can build on their economies of scope to pivot to other products (as they do with gold). Instead, opening options for non-criminal social control is essential for Amazon conservation, which requires much greater coordination and investment, even under relaxed prohibition scenarios. Therefore, robust, transnationally coordinated environmental law enforcement and sustainable, legal economic alternatives are indispensable to protect Amazonian peoples and ecosystems.