Abstract Background Social support is a well-known protective factor against depressive symptoms and substance use problems, but very few studies have examined its protective effects among residents of permanent supportive housing (PSH), a housing program for people with a history of chronic homelessness. We utilized unconditional latent growth curve models (LGCMs) and parallel process growth models to describe univariate trajectories of social support, depressive symptoms, and substance use problems and to examine their longitudinal associations in a large sample of adults residing in PSH. Methods Participants were 653 adult PSH residents in North Texas (56% female; 57% Black; mean age: 51 years) who participated in a monthly health coaching program from 2014 to 2017. Their health behaviors were assessed at baseline and tracked every six months at three follow-up visits. Results Unconditional LGCMs indicated that over time, social support increased, whereas depressive symptoms and substance use problems decreased. However, their rates of change slowed over time. Further, in parallel process growth models, we found that at baseline, individuals with greater social support tended to have less severe depressive symptoms and substance use problems (coefficients: − 0.67, p < 0.01; − 0.52, p < 0.01, respectively). Individuals with a faster increase in social support tended to have steeper rates of reduction in both depressive symptoms (coefficient: − 0.99, p < 0.01) and substance use problems (coefficient: − 0.98, p < 0.01), respectively. Conclusions This study suggests that plausibly, increases in social support, though slowing over time, still positively impact depressive symptoms and substance use problems among PSH residents. Future PSH programs could emphasize social support as an early component as it may contribute to clients’ overall health.