OBJECTIVES: To (i) develop a methodology for using historical and comparative perspectives to inform policy and (ii) provide evidence for antimicrobial-resistance (AMR) policymaking by drawing on lessons from climate change and tobacco control. METHODS: Using a qualitative design, we systematically examined two other complex, large-scale policy issues-climate change and tobacco control-to identify what relevance to AMR can be learned from how these issues have evolved over time. During 2018-2020, we employed a five-stage approach to conducting an exploratory study involving a review of secondary historical analysis, identification of drivers of change, prioritisation of the identified drivers, scenario generation and elicitation of possible policy responses. We sought to disrupt more 'traditional' policy and research spaces to create an alternative where, stimulated by historical analysis, academics (including historians) and policymakers could come together to challenge norms and practices and think creatively about AMR policy design. RESULTS: An iterative process of analysis and engagement resulted in lessons for AMR policy concerning persistent evidence gaps and uncertainty, the need for cross-sector involvement and a collective effort through global governance, the demand for new interventions through more investment in research and innovation, and recognising the dynamic relationship between social change and policy to change people's attitudes and behaviours are crucial towards tackling AMR. CONCLUSION: We draw on new methodological lessons around the pragmatism of future- and policy-oriented approaches incorporating robust historical and comparative analysis. The study demonstrates proof of concept and offers a reproducible method to advance further methodology, including transferrable policies that could tackle health problems, such as AMR.