Background: The locus of control (LOC) construct has been associated with onset, course, and severity of anxiety and depression. We investigated the stability of LOC, the bidirectional relationships between LOC and symptom severity of anxiety and depression over nine years, and the influence of intermediate positive and negative life-events on these associations. Methods: Data came from five assessment waves over nine years of 2052 subjects with an anxiety or depressive disorder or healthy controls. First, the stability of LOC (assessed with 5-item Mastery Scale) was tested. Next, associations between LOC, anxiety severity (Beck Anxiety Inventory), depression severity (Inventory of Depressive Symptomatology), and intermediate positive and negative life-events (20-item List of Threatening Experience Questionnaire) were determined with structural equation modeling. Results: LOC was rather stable over nine years (r = 0.62), and scores increased slightly with age (i.e. became more internal). LOC yielded equal stability estimates as symptom levels of anxiety and depression did over nine years. A more external LOC predicted higher anxiety and depression severity, but did not influence the incidence of positive and negative life-events. Higher depression severity and more negative life-events predicted the development of a more external LOC, whereas more positive life-events predicted a more internal LOC. Anxiety severity had no effect on LOC. Limitations: Life-events were assessed with self-report measures. Conclusions: The prospective associations between LOC and meaningful changes in anxiety and depressive symptom severity and experienced life-events may yield important new insights for clinical interventions.