(1) Background: The efficacy of the Unified Protocol (UP), a transdiagnostic cognitive-behavioral therapy, with trauma-focused exposure has not been sufficiently demonstrated for post-traumatic stress disorder (PTSD) with multiple comorbidities. This study examined the effects of UP treatment with trauma-focused exposure on symptoms of PTSD and comorbidities in a client who was hesitant about exposure. (2) Methods: The client, who had comorbid dysthymia, social anxiety disorder, agoraphobia, and bulimia nervosa, participated in the UP for 20 sessions over 6 months. The principal diagnosis and symptoms of the comorbid disorders were assessed at baseline, post-intervention, and at the 3-month follow-up. This treatment was conducted as part of a clinical study (UMIN000008322). (3) Results: The client showed improvement in the principal diagnosis and symptoms of the comorbid disorders post-intervention compared with baseline and no longer met the diagnostic criteria for any of the disorders. Considerable symptom improvement was observed with imaginal exposure to trauma memories. (4) Conclusions: The UP was an effective alternative treatment for PTSD and symptoms of comorbidities in this client who was hesitant about exposure to traumatic memories, and that the inclusion of trauma-focused exposure provided sufficient therapeutic effects. Further research is needed to examine the generalizability of our findings.