Given the high prevalence and adverse outcomes associated with generalized anxiety disorder (GAD), development and expansion of effective treatment modalities are important. The present study compared the effectiveness of cognitive behavior therapy targeting intolerance of uncertainty (CBT-IU) and selective serotonin reuptake inhibitors (SSRIs) for treating GAD. A total of 30 Iranian patients with GAD (Mage = 25.16 ± 6.73) were randomised to receive either CBT-IU (n = 15) or SSRI (n = 15). Measures included the Structured Clinical Interview for DSM-5 (SCID-5), Penn State Worry Questionnaire (PSWQ), Why Worry-II (WW-II), Intolerance of Uncertainty Scale (IUS), and Negative Problem Orientation Questionnaire (NPOQ). Repeated measures analysis of variance tested differential treatment outcomes. The results of intention-to-treat (ITT) analysis indicated that although both CBT-IU and SSRI were effective treatments for GAD, CBT-IU produced significantly better results than SSRI at post-treatment. This clinical trial provides preliminary cross-cultural support for the treatment of GAD using CBT-IU, with findings suggesting that this non-medication intervention reduces GAD symptoms.