We studied whether patterns of substance use in relation to unemployment vary depending on educational level. Data come from 1,126 community-based young adults in France (18-35 years of age in 2011) and their parents (TEMPO and GAZEL studies). Tobacco use (≥1 cigarette/day, 22.5% prevalence), nicotine dependence (Fagerström test ≥2, 7.1% prevalence), alcohol use (≥2 units/week, 25.3% prevalence), alcohol abuse (WHO AUDIT ≥7 in women and ≥8 in men, 10.8% prevalence), cannabis use (≥1 time, 16.5% prevalence), and cannabis abuse (CAST ≥2, 5.0% prevalence) were assessed by interview. We conducted logistic regression analyses controlled for inverse probability weights of unemployment, calculated based on demographics, negative life events, health, and juvenile and parental characteristics. Compared to participants who were always employed, those who were unemployed and had no higher education were more likely to smoke tobacco (OR: 2.76, 95% CI: 1.86-4.10), to be nicotine dependent (OR: 5.70, 95% CI: 3.03-10.73), to use cannabis (OR: 2.27, 95% CI: 1.42-3.64), and to abuse cannabis (OR: 3.38, 95% CI: 1.63-7.04). Those who were unemployed and had higher education were especially likely to abuse alcohol (OR: 1.89, 95% CI: 1.16-3.09). Increases in unemployment may impact population levels of substance use, particularly in young adults with low educational attainment.