OBJECTIVES To identify the distinct trajectories of sedentary behavior (SB) and explore whether reduced cardiovascular disease (CVD) risk was associated with a distinct trajectory of physical activity (PA). METHODS We analyzed data from 6,425 people who participated in the Korean Health Panel Survey over a period of 10 years. The participants’ self-reported SB and PA were assessed annually, and trajectory groups were identified using a group-based trajectory model for longitudinal data analysis. Logistic regression analysis was performed to assess the association between CVD risk (10-year cumulative incidence) and the trajectories of SB and PA. The adjusted variables included socio-demographic factors, the predisposing diseases of CVD, and baseline health behaviors. RESULTS Trajectory analysis identified 4 SB trajectory groups: SB group 1 (low and slightly increasing trend, 53.1%), SB group 2 (high and rapidly decreasing trend, 14.7%), SB group 3 (high and slightly decreasing trend, 9.9%), and SB group 4 (low and rapidly increasing trend, 22.2%). The 3 PA trajectory groups were PA group 1 (moderate and slightly decreasing trend, 32.1%), PA group 2 (low and slightly decreasing trend, 57.3%), and PA group 3 (maintained inactivity, 10.7%). By the 10-year follow-up, 577 cases of incident CVD had occurred. We also noted a 50% reduction in the risk of CVD when SB group 4 was accompanied by PA group 1 (odds ratio, 0.50; 95% confidence interval, 0.28 to 0.90). CONCLUSIONS Despite increased time spent in SB, maintaining PA about 2 days to 3 days per week reduced the occurrence of CVD.