Pollution caused by anthropogenic chemicals contributes to interlinked planetary crises, together with climate change and biodiversity loss. One of the key treaties adopted to regulate the transboundary movements of hazardous chemicals is the Rotterdam Convention, which created a framework for countries to better handle the international trade of certain hazardous chemicals. To date, research examining the effectiveness of the Convention has been scarce. Here we analysed 66,156 trade records from the United Nations Comtrade database using a workflow that comprehensively addresses data-quality issues in the database. We found that for 46 listed chemicals, at least 64.5 megatonnes were traded in 2004–2019, and illegal trade was prevalent, reaching at least 25,324 trade records and 25.7 megatonnes. For over 70% of the listed chemicals, the Convention has played a positive role, but large-scale trade of some well-known chemicals such as tetraethyl and tetramethyl lead continues. Concerted efforts are warranted to improve how highly hazardous chemicals are traded globally, including enhancing enforcement of the Convention, addressing illegal trade and swiftly listing problematic chemicals (for example, chrysotile asbestos) in the Convention.