Housing insecurity is a persistent issue in marginalized communities. Maternal depression and substance use contribute additional housing risk for vulnerable families. Maternal mental health problems may erode or disrupt social networks, leaving families with fewer supports upon which to rely in a housing crisis. The present study leveraged a large, longitudinal sample of families with children (N = 2,991). Structural equation modeling with latent variables investigated the role of perceived instrumental support in pathways from maternal depression and substance use to risk for housing insecurity over a 10-year period. Results indicated maternal depression was linked directly with housing insecurity (β = 0.16, p < 0.001), as well as indirectly via reduced perceived instrumental support (β = 0.01, p < 0.05). Maternal substance use was not associated either directly or indirectly with housing insecurity. Social support thus emerged as an important mechanism explaining an enduring association between maternal depression and risk for housing insecurity.