Objective Dysregulated children experience significant impairment in regulating their affect, behavior, and cognitions and are at risk for numerous adverse sequelae. The unclear phenomenology of their symptoms presents a barrier to evidence-based diagnosis and treatment. Method The cognitive, behavioral, and psychophysiological mechanisms of dysregulation were examined in a mixed clinical and community sample of 294 children ages 7-17 using the Research Domain Criteria constructs of cognitive control and frustrative nonreward. Results Results showed that caregivers of dysregulated children viewed them as having many more problems with everyday executive function than children with moderate or low levels of psychiatric symptoms; however, during standardized assessments of more complex cognitive control tasks, performance of dysregulated children differed only from children with low symptoms on tests of cognitive flexibility. In addition, when frustrated, dysregulated children performed more poorly on the Go/No-Go Task and demonstrated less autonomic flexibility as indexed by low respiratory sinus arrhythmia and pre-ejection period scores. Conclusion The findings of this study suggest that autonomic inflexibility and impaired cognitive function in the context of frustration may be mechanisms underlying childhood dysregulation.