Objectives Anxiety and depression are the most prevalent disorders observed in health care services and are frequently comorbid with other disorders. Although Cognitive-Behavioral Therapy (CBT) has widely been shown efficacious to treat anxiety and mood disorders, studies that have focused on its effectiveness in the presence of comorbidity have been few and show conflicting results. Thus, the implications of the presence of comorbid disorders for treatment are still unknown. In an attempt to answer these questions, this study explores the impact of comorbidity on CBT for anxiety and mood disorders in a university-based clinic. Methods A total of 293 clients consulting for anxiety and/or mood disorders at the Service de Consultation de l'École de Psychologie de l'Université Laval (SCEP) between 2007 and 2018 took part in the study. Clients were excluded if they presented uncontrolled psychotic, manic or substance abuse symptoms as their principal complaint. Clients without comorbid disorders where compared to clients who had comorbid disorders on different measures before and after receiving therapy to examine if comorbidity had an impact on CBT effectiveness to treat the principal disorder. The impact of treatment on comorbid disorders was also investigated. Effectiveness was assessed on several measures before and after treatment including the severity of diagnoses (measured with a structured interview), anxiety and mood symptoms as well as quality of life. Repeated measures ANOVAs and t-tests were used. Results Before initiating therapy, clients with comorbid disorders had significantly more severe symptoms than clients without comorbid disorders. However, following therapy, both groups had significantly less severe principal disorders and reached a clinically significant change in equivalent proportions. Furthermore, the number and severity of comorbid disorders significantly decreased following therapy. Conclusion These findings suggest that although the presence of comorbid disorders leads to more severe symptoms, it does not affect the effectiveness of CBT for the principal disorder. Furthermore, comorbid disorders improved even though they were not specifically targeted by treatment. In concordance with the literature, it is thus suggested to keep focusing treatment on the principal disorder, whether comorbid disorders are present or not.