Families in which one or more members are undocumented immigrants experience unique hardships. Yet, little is known about stress and substance use among adolescents growing up in these families. The present study examined associations between two sources of adolescent stress (i.e., low parental involvement due to contextual constraints and family economic insecurity) and lifetime alcohol, cigarette, and marijuana use among adolescents in families with undocumented members. The sample was comprised of 102 adolescents (10–18 years old) and one of his or her parents. Participants responded a survey in English or Spanish. Adolescent lifetime use of alcohol, cigarette, and marijuana was 51, 32.4, and 37.3 %, respectively. Chi-square analyses found no significant gender differences in lifetime substance use. Logistic regression models showed that adolescent stress due to hindered parental involvement increased the odds of both lifetime cigarette and marijuana use after controlling for gender, age, linguistic acculturation, familism, parental control, and negative peer affiliation. Being a girl increased the odds of lifetime alcohol use.