Background Obesity is a risk factor for both cardiovascular disease and dementia, but the mechanisms underlying this association are not fully understood. We examined associations between obesity, including estimates of central obesity using different modalities, with brain grey matter (GM) volume in the UK Biobank, a large population-based cohort study. Methods To determine relationships between obesity and the brain we used brain MRI, abdominal MRI, dual-energy X-ray absorptiometry (DXA), and bioelectric whole-body impedance. We determined whether obesity was associated with any change in brain grey matter (GM) and white matter (WM) volumes, and brain network efficiency derived from the structural connectome (wiring of the brain) as determined from diffusion tensor MRI tractography. Using Waist-Hip Ratio (WHR), abdominal MRI and DXA we determined whether any associations were primarily with central rather than peripheral obesity, and whether associations were mediated by known cardiovascular risk factors. We analysed brain MRI data from 15,634. Results We found that central obesity, was associated with decreased GM volume (anthropometric data: p = 6.7 × 10-16, DXA: p = 8.3×10-81, abdominal MRI: p = 0.0006). Regional associations were found between central obesity and with specific GM subcortical nuclei (thalamus, caudate, pallidum, nucleus accumbens). In contrast, no associations were found with WM volume or structure, or brain network efficiency. The effects of central obesity on GM volume were not mediated by C-reactive protein or blood pressure, glucose, lipids. Conclusions Central body fat distribution rather than the overall body-fat percentage is associated with grey matter changes in people with obesity. Further work is required to identify the factors that mediate the association between central obesity and GM atrophy.