Abstract Background Overweight is a major risk factor for non-communicable diseases (NCDs) in Europe, affecting almost 60% of all adults. Tackling obesity is therefore a key long-term health challenge and is vital to reduce premature mortality from NCDs. Methodological challenges remain however, to provide actionable evidence on the potential health benefits of population weight reduction interventions. This study aims to use a g-computation approach to assess the impact of hypothetical weight reduction scenarios on NCDs in Belgium in a multi-exposure context. Methods Belgian health interview survey data (2008/2013/2018, n = 27 536) were linked to environmental data at the residential address. A g-computation approach was used to evaluate the potential impact fraction (PIF) of population weight reduction scenarios on four NCDs: diabetes, hypertension, cardiovascular disease (CVD), and musculoskeletal (MSK) disease. Four scenarios were considered: 1) a distribution shift where, for each individual with overweight, a counterfactual weight was drawn from the distribution of individuals with a “normal” BMI 2) a one-unit reduction of the BMI of individuals with overweight, 3) a modification of the BMI of individuals with overweight based on a weight loss of 10%, 4) a reduction of the waist circumference (WC) to half of the height among all people with a WC:height ratio greater than 0.5. Regression models were adjusted for socio-demographic, lifestyle, and environmental factors. Results The first scenario resulted in preventing a proportion of cases ranging from 32.3% for diabetes to 6% for MSK diseases. The second scenario prevented a proportion of cases ranging from 4.5% for diabetes to 0.8% for MSK diseases. The third scenario prevented a proportion of cases, ranging from 13.6% for diabetes to 2.4% for MSK diseases and the fourth scenario prevented a proportion of cases ranging from 36.4% for diabetes to 7.1% for MSK diseases. Conclusion Implementing weight reduction scenarios among individuals with excess weight ...