Background: Anxiety and depressive disorders in adolescents have an enormous burden worldwide due to their high prevalence and disability. Despite the high comorbidity between these disorders, preventive interventions have often been developed separately for anxiety and depression. Objective: The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents (UP-A; Ehrenreich-May et al. in Unified protocols for transdiagnostic treatment of emotional disorders in children and adolescents, Oxford University Press, New York, 2018), a transdiagnostic treatment that targets core dysfunctions associated with anxiety and depression within a single protocol, was adapted as a universal preventive anxiety and depression program for the purposes of this investigation. The subsequent study of this adapted protocol evaluated pre- to post-intervention changes across a range of primary and secondary outcome measures. The secondary aims of this study were to assess the acceptability and feasibility of the adapted UP-A. Methods: Twenty-eight students (mean age = 14.67; SD = 0.87) participated in this uncontrolled trial conducted in Madrid, Spain. The program included nine weekly 55-min sessions administered in a school setting by an advanced doctoral student in clinical psychology to two groups of 15 and 13 students, respectively. Results: Intent-to-treat analyses revealed significant declines in self-reported anxiety symptoms, interference of anxiety and depression, and top problems' mean severity. Moderate to high participant satisfaction was indicated. Conclusions: The initial promising findings suggest that future trials of the UP-A adapted as a school-based universal anxiety and depression prevention program using a larger sample size are warranted. However, the results of this study should be interpreted cautiously due to limitations regarding the small sample size as well as the lack of a control group and a follow-up period. Suggestions are provided as to how the intervention might be refined in content and delivery.