The role of neighborhood walkability and safety in mediating the association between education and physical activity has not been quantified. We used data from the 2010 and 2012 Communities Putting Prevention to Work Behavioral Risk Factor Surveillance System and structural equation modeling to estimate how much of the effect of education level on physical activity was mediated by perceived neighborhood walkability and safety. Neighborhood walkability accounts for 11.3% and neighborhood safety accounts for 6.8% of the effect. A modest proportion of the important association between education and physical activity is mediated by perceived neighborhood walkability and safety, suggesting that interventions focused on enhancing walkability and safety could reduce the disparity in physical activity associated with education level.