Ultra-processed foods provide 58 % of energy intake and 89 % of added sugars in the American diet. Nevertheless, the association between ultra-processed foods and excess weight has not been investigated in a US sample. The present investigation therefore aims to examine the association between ultra-processed foods and excess weight in a nationally representative sample of US adults. We performed a cross-sectional analysis of anthropometric and dietary data from 15 977 adults (20–64 years) participating in the National Health and Nutrition Examination Survey 2005–2014. Dietary data were collected by 24-h recall. Height, weight and waist circumference (WC) were measured. Foods were classified as ultra-processed/non-ultra-processed according to the NOVA classification. Multivariable linear and logistic regression was used to evaluate the association between ultra-processed food consumption (% energy) and BMI, WC and odds of BMI≥25 kg/m2, BMI≥30 kg/m2 and abdominal obesity (men: WC≥102 cm, women: WC≥88 cm). Prevalence of BMI≥25 kg/m2, BMI≥30 kg/m2 and abdominal obesity was 69·2, 36·1 and 53·0 %, respectively. Consuming ≥74·2 v. ≤36·5 % of total energy from ultra-processed foods was associated with 1·61 units higher BMI (95 % CI 1·11, 2·10), 4·07 cm greater WC (95 % CI 2·94, 5·19) and 48, 53 and 62 % higher odds of BMI≥25 kg/m2, BMI≥30 kg/m2 and abdominal obesity, respectively (OR 1·48; 95 % CI 1·25, 1·76; OR 1·53; 95 % CI 1·29, 1·81; OR 1·62; 95 % CI 1·39, 1·89, respectively; Pfor trend<0·001 for all). A significant interaction between being female and ultra-processed food consumption was found for BMI (F4,79=4·89, P=0·002), WC (F4,79=3·71, P=0·008) and BMI≥25 kg/m2 (F4,79=5·35, P<0·001). As the first study in a US population, our findings support that higher consumption of ultra-processed food is associated with excess weight, and that the association is more pronounced among women.