Postpartum mood disorders (PPMD) affect approximately 10-20% of women and have adverse consequences for both mom and baby. Lifetime substance use has received limited attention in relation to PPMD. The present study examined associations of lifetime alcohol and drug use with postpartum mental health problems. Women (n = 100) within approximately 3 months postpartum (M = 2.01, SD = 1.32) participated in semi-structured interviews querying lifetime substance use, mental health history, and postpartum symptoms of anxiety, stress, posttraumatic stress disorder (PTSD), depression, and obsessive compulsive disorder. The study was conducted in an urban Canadian city from 2009 to 2010. Analyses revealed that lifetime substance use increased the variability explained in postpartum PTSD (p = .011), above and beyond sociodemographic characteristics and mental health history. The same trend, though not significant, was observed for stress (p = .059) and anxiety (p = .070). Lifetime drug use, specifically, was associated with postpartum stress (p = .021) and anxiety (p = .041), whereas lifetime alcohol use was not (ps ≥ .128). Findings suggest that lifetime drug use is associated with PPMD. Future research should examine whether screening for lifetime drug use during antenatal and postpartum care improves identification of women experiencing PPMD.