Researchers have seldom examined whether risk and protective factors are consistently linked to substance use across historical time. Using nationally representative data collected from 22 consecutive cohorts of high school seniors (approximate N = 188,000) from the Monitoring the Future (MTF) project, we investigated whether correlates of substance use changed across historical time. We found a high degree of consistency across historical time in predictors of past month cigarette use, past month alcohol use, past year marijuana use, and past year cocaine use. Some predictors such as religiosity, political beliefs, truancy, and frequent evenings out were consistently linked to substance use. The consistency of other predictors such as region, parental education, and college plans was contingent in part upon historical time period, the particular substance, and its level of use.