Various studies found personality to be related to substance use, but little attention is paid to the role of personality risk dimensions with regard to an early onset of alcohol, tobacco, and marijuana use. Therefore, the current study used a variable-centered approach to examine whether anxiety sensitivity, hopelessness, sensation seeking, and impulsivity predict the onset of alcohol, tobacco, and marijuana use in early adolescence. Additionally, we adopted a person-centered approach to examine whether different personality subgroups could be identified, and whether these subgroups would be predictive of substance use. For that purpose, longitudinal data of a broader effectiveness study were used from 758 early adolescents (53 % female) aged 11–14 years. Structural equation models showed that hopelessness and sensation seeking were predictive of having ever used alcohol and tobacco. Also, sensation seeking was predictive of marijuana use. Latent profile analyses on the first wave data revealed a three-profile solution for boys (i.e., resilients, internalizers, and externalizers) and a two-profile solution for girls (i.e., resilients and internalizers). In contrast to our expectation, further analyses revealed no significant differences in substance use between the different subprofiles for both boys and girls. The separate personality dimensions thus seem more relevant in predicting the onset of substance use compared to the personality profiles. However, the personality profiles might be informative in explaining more excessive substance use behaviors.