Objective: This study examined cross-informant evidence for a general factor of psychopathology (‘P’) and a narrower, clinically oriented dysregulation general factor based on the Dysregulation Profile (‘DP’) in a large clinical sample of children and adolescents. We also compared the magnitude of P and DP general factor associations with self-harm and suicidal ideation as an indicator of criterion validity. Itemwise data from the Child Behavior Checklist (N = 2934; 4-18 years of age) were analyzed using confirmatory bifactor modeling and replicated in a supplementary analysis using Youth Self Report data (N = 2,395). Method: Itemwise data from the Child Behavior Checklist (N = 2,934; 4-18 years of age) were analyzed using confirmatory bifactor modeling and replicated in a supplementary analysis using Youth Self Report data (N = 2,395). Results: General P and DP bifactor models fit the data better than single-factor and correlated factor models. Cross-informant criterion analyses on a subset of youth (n ¼ 1,552) suggested that whether modeled as latent P or DP, associations with a brief composite index of self-harm and suicidal ideation are essentially of the same magnitude. Conclusion: Our findings provide novel, large-sample support for the existence of general factors of psychopathology and dysregulation in clinically referred children and adolescents using a standardized rating system of psychopathology symptoms. Moreover, our results provide preliminary evidence that general psychopathology and dysregulation factors are clinically meaningful constructs. In addition, our findings raise the possibility that the DP general factor may serve as an efficient proxy for the general psychopathology factor in future clinical applications. Further efforts are necessary to understand the core empirical meaning of the P factor and to determine how it can be applied to clinical assessment and intervention.