Objective: We present the prevalence and incidence rates of alcohol, nicotine, and illicit substance use, abuse, and dependence in a sample of German adolescents and young adults. Patterns of onset, cohort trends, and use of various substance classes are also analyzed. Method: A prospective longitudinal epidemiological study with a representative sample of adolescents and young adults (n = 3,021; baseline age range = 14–24 years) was conducted in Munich, Germany. Participants were assessed between 1995 and 1999 with the Munich-Composite International Diagnostic Interview. Results: Cumulative lifetime incidence (up to age 28) of any substance abuse or dependence was 43.8%, and 12-month prevalence of any substance abuse or dependence was 24.4%. The lifetime incidence of nicotine dependence was most frequent (24.8%), followed by alcohol abuse (19.3%) and alcohol dependence (9.2%); 61.7% endorsed the regular use of a substance for at least one circumscribed period during their lifetime. Age-specific incidence rates and age at onset of substance use disorders differed by age cohorts. Furthermore, nicotine dependence was significantly associated with illicit substance use disorders (HR = 2.6, 95% CI 1.7–4.0). An interactive relationship between age, age at onset of nicotine dependence, and subsequent onset of illicit substance use disorders was found. Conclusions: Since the baseline investigation in 1995, high incidence rates of substance use disorders and substance use have been observed in this young German sample. Especially younger cohorts report significantly earlier ages at onset of abuse and dependence. There also seems to be a trend towards a secondary age at onset peak of nicotine dependence after the onset of illicit drug use disorders. Further investigations are needed to study these patterns in younger samples. However, results emphasize the need for a combined prevention of illicit drugs and nicotine dependence.