This study aimed to resolve the direction of the relation between Greek affiliation and substance use by taking advantage of the quasi-experimental nature of change in college fraternity/sorority affiliation. Precollege individual differences and college substance use were examined as a function of time-varying Greek status to characterize self-selection (by which heavy substance users opt into Greek systems) and socialization (by which Greek systems foster heavy substance use). Prospective data on continuously enrolled college students (N = 2,376), assessed at precollege and in the first 6 semesters of college, were used. Latent class analysis indicated 4 discrete groups of status: constant Greek members (30%), constant nonmembers (64%), late joiners (2%), and droppers (4%). Random coefficient models demonstrated disaffiliation with Greek systems is associated with decreases in risky drinking and alcohol-conducive environmental factors (peer norms and alcohol availability), whereas affiliation is associated with increases, indicating Greek socialization via sociocognitive and physical environments. Future Greeks differed from nonmembers in diverse individual characteristics and heavier substance use at precollege, suggesting multiple selection paths into Greek systems. Findings suggest a reciprocal relation between Greek environment and individuals in determining the trajectories of college drinking and heterogeneity in drinking as functions of changes in Greek affiliation.