BACKGROUND: The UK is legally committed to reduce its greenhouse gas emissions to net zero by 2050. We aimed to understand the potential impact on population health of two pathways for achieving this target through the integrated effects of six actions in four sectors. METHODS: In this multisectoral modelling study we assessed the impact on population health in England and Wales of six policy actions relating to electricity generation, transport, home energy, active travel, and diets relative to a baseline scenario in which climate actions, exposures, and behaviours were held constant at 2020 levels under two scenarios: the UK Climate Change Committee's Balanced Pathway of technological and behavioural measures; and its Widespread Engagement Pathway, which assumes more substantial changes to consumer behaviours. We quantified the impacts of each policy action on mortality using a life table comprising all exposures, behaviours, and health outcomes in a single model. FINDINGS: Both scenarios are predicted to result in substantial reductions in mortality by 2050. The Widespread Engagement Pathway achieves a slightly greater reduction in outdoor fine particulate matter air pollution of 3·2 μg/m3 (33%) and, under assumptions of appropriate ventilation, a greater improvement in indoor air pollution (a decrease in indoor-generated fine particulate matter from 9·4 μg/m3 to 4·6 μg/m3) and winter temperatures (increasing from 17·8°C to 18·1°C), as well as appreciably greater changes in levels of active travel (27% increase in metabolic equivalent hours per week of walking and cycling) by 2050. Additionally, the greater reduction in red meat consumption (50% compared with 35% under the Balanced Pathway) by 2050 results in greater consumption of fruits (17-18 g/day), vegetables (22-23 g/day), and legumes (5-7 g/day). Combined actions under the Balanced Pathway result in more than 2 million cumulative life-years gained over 2021-50; the estimated gain under the Widespread Engagement Pathway is greater, corresponding to nearly 2·5 million life-years gained by 2050 and 13·7 million life-years gained by 2100. INTERPRETATION: Reaching net zero greenhouse gas emissions is likely to lead to substantial benefits for public health in England and Wales, with the cumulative net benefits being correspondingly greater with a pathway that entails faster and more ambitious changes, especially in physical activity and diets. FUNDING: National Institute for Health Research and the Wellcome Trust.