OBJECTIVE: To investigate the causal effects of physical activity and sedentary traits on risk of Age-related macular degeneration (AMD). METHODS: A two-sample Mendelian randomization (MR) analysis was used to investigate the causal relationship between physical activity and risk of AMD. We used genome-wide association studies (GWAS) summary statistics from two publicly available biobank-scale cohorts: UK Biobank and FinnGen. Physical activity data were self-reported by 703,901 UK Biobank participants and sedentary behaviour data were gathered from 159,606 FinnGen participants. Our analysis primarily used the inverse variance weighted (IVW) method. RESULT: Engaging in moderate-to-vigorous physical activity significantly reduced the risk of AMD with an odds ratio of 0.77 (95% CI: 0.66-0.89). However, leisure screen time showed a slight but non-statistically significant upward trend. Sedentary behaviour at work, sedentary commuting showed no causal effects on AMD risk. CONCLUSIONS: This study used MR analysis to examine the causal relationship between physical activity, sedentary behaviour, and AMD. It offers genetic evidence suggesting that physical activity may protect against AMD, emphasizing the significance of lifestyle factors in maintaining ocular health.