The purpose of this study was to elucidate the association between weight cycling and clinical outcomes such as type 2 diabetes and hypertension with differential effects of baseline age and obesity. Nationwide data from 6,132,569 healthy adults who underwent five or more health screenings between 2002 and 2011 were analyzed and followed until December 2019 for type 2 diabetes and hypertension. Weight cycling was defined as a change in body weight followed by another change in the opposite direction. Through the Cox proportional hazards model, the number and degree of weight cycles were positively associated with increased risk of type 2 diabetes and hypertension. The hazard ratios (HRs) of weight cycling for type 2 diabetes and hypertension were as high as 1.263 (1.213–1.315) and 1.175 (1.144–1.207) at two or more weight cycles of 10% of body weight (BW), respectively. The association was stronger for females, individuals with normal body weight/BMI, and older individuals. Weight cycling was significantly associated with an increased risk of adverse health outcomes and was stronger in individuals with normal BMI and females, indicating that these people should be informed about the potential risk of weight cycling.