Background: Promoting active modes of transportation such as cycling may generate important public health, economic, and climate mitigation benefits. We aim to assess the mortality and morbidity impacts of cycling in a country with relatively low levels of cycling, France, along with associated monetary benefits. We further assess the potential additional benefits of shifting a portion of short trips from cars to bikes, including projected greenhouse gas emissions savings. Methods: Using individual data from a nationally representative mobility survey, we described the French 2019 cycling levels by age and sex. We conducted a burden of disease analysis to assess the incidence of five chronic diseases (breast cancer, colon cancer, cardiovascular diseases, dementia, and type-2 diabetes) and the number of deaths prevented by cycling, based on national incidence and mortality data and dose–response relationships from meta-analyses. We assessed the corresponding direct medical cost savings and the intangible costs prevented based on the value of a statistical life year. Lastly, based on individual simulations, we assessed the likely additional benefits of shifting 25% of short (<5 km) car trips to cycling. Findings: The French adult (20–89 years) population was estimated to cycle on average 1 min 17 sec pers−1 day−1 in 2019, with important heterogeneity across sex and age. This yielded benefits of 1,919 (uncertainty interval, UI: 1,101–2,736) premature deaths and 5,963 (UI: 3,178–8,749) chronic disease cases prevented, with males reaping nearly 75% of these benefits. Direct medical costs prevented were estimated at €191 million (UI: 98–285) annually, while the corresponding intangible costs were nearly 25 times higher (€4.8 billion, UI: 3.0–6.5). We estimated that on average, €1.02 (UI: 0.59–1.62) of intangible costs were prevented for every km cycled. Shifting 25% of short car trips to cycling would yield approximatively a 2-fold increase in deaths prevented, while also generating important CO2 emissions reductions (0.257 MtCO2e, UI: 0.231–0.288). Interpretation: In a country with a low- to moderate-cycling culture, cycling already generates important public health and health-related economic benefits. Further development of active transportation would increase these benefits while also contributing to climate change mitigation targets.