Abstract. Background:. Physical activity, sedentary behavior (SB), and sleep duration are associated with brain health. Effects of those on developing Parkinson’s disease (PD) are poorly investigated. This study aimed to examine the independent and joint associations of physical activity, SB, sleep with PD risk. Methods:. We analyzed data on 401,697 participants from the UK Biobank cohort, which was enrolled in 2006–2010. Physical activities were measured based on a questionnaire. Sleep and SB time were defined through self-reported total number of hours. Models fitted with restricted cubic spline were conducted to test for linear and non-linear shapes of each association. Cox proportional hazards regression models were used to estimate the association of three modifiable behaviors. Results:. Our analytic sample included 401,697 participants with 3030 identified cases of PD (mean age, 63 years; 62.9% male). PD risk was 18% lower in the high total physical activity group (95% CI, 0.75–0.90), 22% lower in the high leisure-time physical activity (LTPA) group (95% CI, 0.71–0.86) compared with the low level and 14% higher in the high sleep duration group (95% CI, 1.05–1.24) compared to moderate group. Total SB time was irrelevant with PD risk, while high TV viewing showed a 12% increase of PD risk compared to the low group (95% CI, 1.02–1.22). Low computer use (0 h/day) was associated with a 14% higher risk compared to 1 h/day use (95% CI, 1.04–1.26). Those associations were independent. A combination of 7 h/day sleep, moderate-to-high computer use, and moderate-to-vigorous intensity of LTPA showed lowest PD risk (HR, 0.70; 95% CI, 0.57–0.85). Conclusions:. Physical activity, SB, and sleep were associated with PD risks separately. Our findings emphasize the possibility for changing these three daily activities concurrently to lower the risk of PD. These findings may promote an active lifestyle for PD prevention.