Evidenced-based practices are extremely valuable in the field of psychology. Randomized clinical trials have been considered the gold standard of evaluating the effectiveness of treatments. However, the importance of single-subject design and its focus on individual differences to understanding what therapeutic interventions works for whom offers complementary evidence. This study examined the efficacy of brief psychodynamic therapy using Luborsky’s (1999) core conflictual relationship theme (CCRT) approach with two clinical case studies in the treatment of major depressive disorder and generalized anxiety disorder. The participants were selected based on convenience sampling. A single-subject method with time series data was utilized. Statistical methods of Percentage of Non-Overlapping Data (PND) and Reliable Change Index (RCI) were used for analysis. Outcome measures used to assess change across treatment included the Brief Symptom Inventory (BSI) and Participant Health Questionnaire-depression and anxiety disorders (PHQ-SADS). The results of the present study indicate that CCRT approach provided clinically significant improvement for depression and anxiety concerns for both clients. All areas of functioning assessed using BSI and PHQ-SADS demonstrated significant and positive changes.