AimThis study investigated the depot‐ and sex‐specific associations of adiposity indicators with incident multimorbidity and comorbidity pairs.Materials and MethodsWe selected 382 678 adults without multimorbidity (≥2 chronic diseases) at baseline from the UK Biobank. General obesity, abdominal obesity and body fat percentage indices were measured.ResultsCox proportional hazard regression analyses of general obesity indices revealed that for every one‐unit increase in body mass index, the risk of incident multimorbidity increased by 5.2% (95% confidence interval 5.0%‐5.4%). A dose‐response relationship was observed between general obesity degrees and incident multimorbidity. The analysis of abdominal obesity indices showed that for every 0.1 increment in waist‐to‐height ratio and waist‐to‐hip ratio, the risk of incident multimorbidity increased by 42.0% (37.9%‐46.2%) and 27.9% (25.7%‐30.0%), respectively. Central obesity, as defined by waist circumference, contributed to a 23.2% increased risk of incident multimorbidity. Hip circumference and hip‐to‐height ratio had protective effects on multimorbidity onset. Consistent findings were observed for males and females. Body fat percentage elevated 3% (0.2%‐5.9%) and 5.3% (1.1%‐9.7%) risks of incident multimorbidity in all adults and females, respectively. Arm fat percentages elevated 5.3% (0.8%‐9.9%) and 19.4% (11.0%‐28.5%) risks of incident multimorbidity in all adults and males, respectively. The general obesity indices, waist circumference, waist‐to‐height ratio, waist‐to‐hip ratio and central obesity increased the onset of comorbidity pairs, whereas hip circumference and hip‐to‐height ratio decreased the onset of comorbidity pairs. These adiposity indicators mainly affect diabetes mellitus‐related comorbidity onset in males and hypertensive‐related comorbidity onset in females.ConclusionsAdiposity indicators are predictors of multimorbidity and comorbidity pairs and represent a promising approach for intervention.