Maladaptive personality, the motivational systems, and intolerance of uncertainty play important roles in the statistical explanation of depression and anxiety. Here, we notably examined for the first time whether symptoms of depression, anxiety, health anxiety, and fear of COVID-19 share similar associations (e.g., variance explained) with these important dispositional dimensions. For this cross-sectional study, data from 1001 participants recruited in Germany (50% women; mean age = 47.26) were collected. In separate models, we examined the cross-sectional associations of the symptoms of depression, anxiety, health anxiety, and fear of COVID-19 with the Personality Inventory for DSM Short Form Plus scales, the Behavioral Inhibition System / Flight-Fight-Freeze System / Behavioral Activation System scales, and Intolerance of Uncertainty scales. Relative weight analyses were used to determine the within-model importance of the different scales in the prediction of the symptoms. All in all, our study showed that maladaptive personality and intolerance of uncertainty dimensions are more important sets of predictors of the studied outcomes (with which depressive and anxious symptomatology feature very similar associations) than are the motivational system dimensions. Within predictor sets, the scales with the most important predictors were: Negative Affectivity, the Behavioral Inhibition System, and Burden due to Intolerance of Uncertainty. Our findings highlight the relevance of focusing behavioral targets of psychotherapy on these within-set traits and identify potential research priorities (maladaptive personality and intolerance of uncertainty) in relation to the symptoms of interest.