Abstract Background Although obesity has emerged as a global pandemic, the evidence for identifying optimal residential density in relation to obesity has been far from compelling. High residential density may be hypothesized to constitute leptogenic multifunctional environments promoting active living. We aimed to examine the association between adiposity and housing unit density. Methods This cross-sectional study involved 450 433 adults aged 38–73 years with full data from the UK Biobank. Residential unit density was objectively assessed within a 1 km street-network catchment of participants' residence. Other activity-influencing built environment included density of retail, public transport, and street movement density modelled from network analyses of through-movement of street links within the defined catchment. We fitted linear and non-linear (restricted cubic spline) models after adjusting for activity-influencing built environment, neighbourhood deprivation, socio-demographics, lifestyle, and co-morbidities, and we investigated effect modification by sex, age, and physical activity. Findings A restricted cubic spline model with three knots best fitted the data and identified two inflexion points at residential densities of 1600 and 3400 units per km 2 . Below a density of 1600 units per km 2 , each increment of 1000 units per km 2 was significantly associated with higher body-mass index (BMI) (β=0·24, 95% CI 0·19 to 0·30), higher waist circumference (WC) (0·55, 0·40 to 0·69), higher whole body fat (WBF) (0·57, 0·46 to 0·68), and increased odds of obesity (odds ratio 1·13, 95% CI 1·09 to 1·13); between 1600 and 3400 units per km 2 , it was associated with lower BMI (−0·13, −0·18 to −0·08), lower WC (−0·19, −0·32 to −007), lower WBF (−0·20, −0·30 to −0·10), and lower odds of obesity (0·96, 0·94 to 0·99); and above 3400 units per km 2 , it was leptogenic, being associated with lower BMI (−0·15, −0·19 to −0·11), lower WC (−0·50, −0·60 to −0·40), lower WBF (−0·26, −0·34 to −0·18), and lower odds of obesity (0·93, 0·91 to 0·95). Stronger leptogenic effects of housing density were observed among younger participants, female participants, and participants engaging higher physical activity. Interpretation High residential density is associated with lower adiposity in a large and diverse population sample. The evidence points to the value of housing and land-use planning policy related to densification as an upstream-level candidate for public health intervention against adiposity. Further longitudinal evidence is needed to establish causality. Funding University of Hong Kong Research Assistant Professorship grant, UK Biobank seed grant, UK Economic and Social Research Council Transformative Research grant (ES/L003201/1).