There is strong evidence for a general psychopathology dimension which captures covariance among all forms of psychopathology, yet its nature and underlying association with personality remain unclear. This study examined the co-development of general psychopathology and four high-risk personality traits: anxiety sensitivity, negative thinking, sensation seeking, and impulsivity. Data from two large Australian school-based randomised controlled trials of substance use prevention programs were analysed (N = 2,083, mean age at baseline = 13.49 years). Adolescents completed self-report measures of psychopathology symptoms and personality at baseline, one-, two-, and three-years post-baseline. Latent curve models with structured residuals, were used to examine the co-development of general psychopathology (extracted from a higher-order model) and personality traits from 13 to 16 years of age, controlling for age, sex, and cohort. Higher than usual levels of anxiety sensitivity and impulsivity were associated with higher than usual levels of general psychopathology at subsequent time points, and higher than usual levels of general psychopathology were associated with higher than usual levels of negative thinking at later time points. Sensation seeking was unrelated to general psychopathology. These findings enhance our understanding of the meaning and validity of general psychopathology, highlighting potential personality-based prevention and intervention targets.