The effects of macronutrient intake on obesity are controversial. This research aims to investigate the associations between macronutrient intake and new-onset overweight/obesity. The relationship between the consumption of carbohydrate and total fat and obesity was assessed by the multivariable Cox model in this 11-year cohort, which included 6,612 adults (3,321 women and 3,291 men) who were free of overweight and obesity at baseline. The dietary intake was recorded using a 24-h recall method for three consecutive days. Moreover, substitution models were developed to distinguish the effects of macronutrient composition alteration from energy intake modification. During 7.5 person years (IQR 4.3-10.8) of follow-up, 1,807 participants became overweight or obesity. After adjusting for risk factors, the HR of overweight/obesity in extreme quintiles of fat was 1.48 (quintile 5 vs quintile 1, 95% CI, 1.16-1.89; Ptrend =0.02) in women. Additionally, replacing 5% of energy from carbohydrate with equivalent energy from fat was associated with an estimated 4.3% (HR, 1.043; 95% CI, 1.007-1.081) increase in overweight/obesity in women. Moreover, dietary carbohydrate was inversely associated with overweight/obesity (quintile 5 vs quintile 1, HR, 0.70; 95% CI, 0.55-0.89; Ptrend =0.02) in women. Total fat was related to a higher risk of overweight/obesity, whereas high carbohydrate intake was related to a lower risk of overweight/obesity in women, which was not observed in men.