In this study, we examined the unique associations between functional impairment and different psychopathology domains across childhood and adolescence. We examined whether functional impairment’s associations with psychopathological domains can offer important insights to understanding direct and indirect pathways for the co-occurrence among mental health difficulties across childhood and adolescence. From the population-based study Spit for Science, we included 5163 participants between the ages of 6 and 18.97 years (Mean age = 9.98, SD = 2.89) with parent/self-rated quantitative measures of psychopathology. We used network estimation to examine the unique associations among ratings of functional impairment, inattention, hyperactivity, autism, obsessions and compulsions, depression, anxiety, and irritability, while accounting for age effects. Bootstrapped difference tests of edges (partial correlations between two domains in a network) and node (domains/variable within a network) influence on network connectivity were conducted. In addition to domain specific associations, functional impairment-irritability and functional impairment-depression ratings were two of the strongest connections in the network. Overall, functional impairment and depression ratings had some of the highest centrality indices, in terms of their strength and number of direct and indirect connections. Age effects varied in the network with the positive age-depressive ratings connection being the strongest. This study demonstrates the importance of examining associations among psychopathology domains together with functional impairment to delineate important direct and indirect pathways for co-occurrence. We offer data driven hypotheses for impairment-related pathways and suggest important targets for intervention that can be examined in clinical research to mitigate comorbidities.