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This longitudinal study applied general strain theory to elaborate specific stressful events' lagged effects on risk of illicit substance use among non-Hispanic White, non-Hispanic Black, and Hispanic adolescents, and relatedly evaluated the moderating role of race/ethnicity in explaining illicit use. Data were drawn from five waves representing 9 years (2002–2010) of the 1997 National Longitudinal Survey of Youth (NLSY), totaling 16,868 person-waves, and we engaged temporal ordering and generalized estimating equations (GEE) for panel data in STATA for data analysis. Results showed specific events affected risk of illicit substance use differentially across racial/ethnic groups. Strains commonly encountered in disorganized spaces affected non-Hispanic White's risk. Measured strains did not affect non-Hispanic Black respondents and findings for Hispanic respondents point to the family as a possible strain. Results indicated legal drug use and depression increased risk of illicit use greatly. Race/ethnicity's role in illicit use's associations with several variables illustrates differential implications for racial/ethnic groups in policy and preventive interventions.