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Aims: The United Kingdom and Australia have developed highly divergent policy responses to electronic nicotine delivery systems (ENDS). To understand the historical origins of these differences, we describe the history of tobacco control in each country and the key roles played in setting ENDS policy in its early stages by public health regulations and policy networks, anti‐smoking organizations, 'vaper' activist networks and advocates of harm reduction policies towards injecting drug use. Methods: We analysed key government reports, policy statements from public health bodies and non‐government organizations (e.g. cancer councils and medical organizations) on ENDS; submissions to an Australian parliamentary inquiry; media coverage of policy debates in medical journals; and the history of tobacco control policy in Australia and England. Key discourses about ENDS were identified for each country. These were compared across countries during a multi‐day face‐to‐face meeting, where consensus was reached on the key commonalities and divergences in historical approaches to nicotine policy. This paper focuses on England, as different policy responses were apparent in constituent countries of the United Kingdom, and Scotland in particular. Results: Policymakers in Australia and England differ markedly in the priority that they have given to using ENDS to promote smoking cessation or restricting smokers' access to prevent uptake among young people. In understanding the origins of these divergent responses, we identified the following key differences between the two countries' approaches to nicotine regulation: an influential scientific network that favoured nicotine harm reduction in the United Kingdom and the absence of such a network in Australia; the success of different types of health activism both in England and in Europe in opposing more restrictive policies; and the greater influence on policy in England of the field of illicit drug harm reduction. Conclusions: An understanding of the different policy responses to electronic nicotine delivery systems (ENDS) in England and Australia requires an appreciation of how actors within the different policy structures, scientific networks and activist organizations in each country and region have interpreted the evidence and the priority that policymakers have given to the competing goals of preventing adolescent uptake and encouraging smokers to use ENDS to quit smoking. [ABSTRACT FROM AUTHOR]