Introduction Chronic diseases are the leading causes of death in the United States and have been associated with depressive symptoms and poor health-related quality of life (HRQOL). This study examined whether depressive symptoms and HRQOL indicators changed among participants in Pasos Adelante, a chronic disease prevention and control program implemented in a US–Mexico border community. Methods Pasos Adelante was a 12-week promotora-led program that included educational sessions and walking groups. We used the Centers for Epidemiologic Studies Depression Scale (CES-D) and the Center for Disease Control's "Healthy Days" measures to measure depressive symptoms and HRQOL. We used linear mixed-effects models and general estimating equations to analyze changes in CES-D scores and HRQOL indicators from baseline to postprogram and from postprogram to 3-month follow-up. Results At baseline, participants had a mean of 7.1 physically unhealthy days, 7.4 mentally unhealthy days, and 3.9 days of activity limitation. The mean number of physically and mentally unhealthy days declined significantly from baseline to postprogram, but the mean number of activity limitation days did not. At baseline, 42.6% of participants reported their health as fair/poor; 20.8% of participants reported frequent mental distress, and 31.8% had a CES-D score of 16 or more. All 3 proportions declined from baseline to postprogram. No significant changes occurred between postprogram and follow-up. Conclusion Participants in Pasos Adelante showed improvement in depressive symptoms and several HRQOL indicators. Future studies should use an experimental design with a comparison group to determine whether these findings can be replicated and to examine potential mediators and moderators of program effects.