Introduction: Little research on the association of neighborhood environment with physical activity in resource-poor communities has been done. This study assessed changes in perceptions of the neighborhood environment and the association between those perceptions and physical activity in Mexican Americans on the Texas–Mexico border in an area where there would be community efforts to enhance pedestrian and cycling infrastructure and programming. Methods: We analyzed data from a population-based cohort of Mexican American individuals on the Texas–Mexico border. From 2008 to 2018, interviewer-administered questionnaires were used to collect perceptions of neighborhood environment and physical activity at baseline, 5- and 10-year follow-ups, and at other ancillary study visits, with an average of 3 data points per participant. We conducted multivariable longitudinal logistic regression analyses to assess if the changes in odds of positive perceptions of the neighborhood environment over the study years differed by physical activity patterns. Results: The sample (n = 1036) was mostly female (71%), born in Mexico (70%), and had no health insurance (69%). We saw improvements in the perceptions of several neighborhood environment attributes from 2008 to 2018, though we saw different longitudinal trajectories in these perceptions based on an individual’s longitudinal physical activity patterns. By 2014–2018, we saw significantly higher positive perceptions of the neighborhood environment for those who consistently met physical activity guidelines compared with those who did not (adjusted rate ratio = 1.12, P = .049). Discussion: We found that perceptions of many neighborhood environment attributes improved between 2008 and 2018, and that overall positive perceptions were associated with consistently meeting physical activity guidelines over time.