Background The current study tested whether perceived social support serves as a mediator of anxiety and depressive symptom change following evidence‐based anxiety treatment in the primary care setting. Gender, age, and race were tested as moderators. Methods Data were obtained from 1004 adult patients (age M = 43, SD = 13; 71% female; 56% White, 20% Hispanic, 12% Black) who participated in a randomized effectiveness trial (coordinated anxiety learning and management [CALM] study) comparing evidence‐based intervention (cognitive‐behavioral therapy and/or psychopharmacology) to usual care in the primary care setting. Patients were assessed with a battery of questionnaires at baseline, as well as at 6, 12, and 18 months following baseline. Measures utilized in the mediation analyses included the Abbreviated Medical Outcomes (MOS) Social Support Survey, the Brief Symptom Index (BSI)–Somatic and Anxiety subscales, and the Patient Health Questionnaire (PHQ‐9). Results There was a mediating effect over time of perceived social support on symptom change following treatment, with stronger effects for 18‐month depression than anxiety. None of the mediating pathways were moderated by gender, age, or race. Conclusions Perceived social support may be central to anxiety and depressive symptom changes over time with evidence‐based intervention in the primary care setting. These findings possibly have important implications for development of anxiety interventions.