There is limited empirical evidence to support the protective effects of physical activity in the prevention of hypertension among African Americans. The purpose of this study was to examine the association of physical activity with incident hypertension among African Americans. We studied 1311 participants without hypertension at baseline enrolled in the Jackson Heart Study, a community-based study of African Americans residing in Jackson, Mississippi. Overall physical activity, moderate-vigorous physical activity, and domain-specific physical activity (work, active living, household, and sport/exercise) were assessed by self-report during the baseline examination (2000-2004). Incident hypertension, assessed at examination 2 (2005-2008) and examination 3 (2009-2013), was defined as the first visit with systolic/diastolic blood pressure ≥140/90 mm Hg or self-reported antihypertensive medication use. Over a median follow-up of 8.0 years, there were 650 (49.6%) incident hypertension cases. The multivariable-adjusted hazard ratios (95% confidence interval) for incident hypertension comparing participants with intermediate and ideal versus poor levels of moderate-vigorous physical activity were 0.84 (0.67-1.05) and 0.76 (0.58-0.99), respectively (P trend=0.038). A graded, dose-response association was also present for sport/exercise-related physical activity (Quartiles 2, 3, and 4 versus Quartile 1: 0.92 [0.68-1.25], 0.87 [0.67-1.13], 0.75 [0.58-0.97], respectively; P trend=0.032). There were no statistically significant associations observed for overall physical activity, or work, active living, and household-related physical activities. In conclusion, the results of the current study suggest that regular moderate-vigorous physical activity or sport/exercise-related physical activity may reduce the risk of developing hypertension in African Americans.