Having poor mental health can be life-threatening, and problems tied to it are prevalent in communities across the United States (US). The city of Austin is one of the ten cities in the US undergoing rapid urban gentrification; however, there is insufficient empirical evidence on the impact of this process on residents’ health. Consequently, this study explored the concept of weathering and life course perspective using data of 331 residents recruited from two regions endemic with gentrification to assess the health impacts of gentrification. We used a triangulation method including univariate, bivariate correlation, and multiple linear regression implemented through the structural equation model to examine the complex pathways to three health outcomes—measured stress, self-rated mental health, and depression symptoms. Bivariate Pearson’s correlation indicated a significant positive association between gentrification score and mental health symptoms and stress. However, the direct association between gentrification and depression disappeared in the causal/path model. In support of the weathering hypothesis, this study found that stress score was directly related to the adulthood depression score. Therefore, this research builds on the accumulating evidence of environmental stress and mental health in the US’s rapidly changing physical and sociocultural environment. Hence, implementing and guaranteeing social equity of resources will improve residents’ health and reduce the cost of health care spending at both the household level and the city government level.