Cognitive behavioral therapy (CBT) is often recommended as a first-line treatment in depression. However, access to CBT remains limited, and up to 50% of patients do not benefit from this therapy. Identifying biomarkers that can predict which patients will respond to CBT may assist in designing optimal treatment allocation strategies. In a Canadian Biomarker Integration Network for Depression (CAN-BIND) study, forty-one adults with depression were recruited to undergo a 16-week course of CBT with thirty having resting-state electroencephalography (EEG) recorded at baseline and week 2 of therapy. Successful clinical response to CBT was defined as a 50% or greater reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to post-treatment completion. EEG relative power spectral measures were analyzed at baseline, week 2, and as early changes from baseline to week 2. At baseline, lower relative delta (0.5–4 Hz) power was observed in responders. This difference was predictive of successful clinical response to CBT. Furthermore, responders exhibited an early increase in relative delta power and a decrease in relative alpha (8–12 Hz) power compared to non-responders. These changes were also found to be good predictors of response to the therapy. These findings showed the potential utility of resting-state EEG in predicting CBT outcomes. They also further reinforce the promise of an EEG-based clinical decision-making tool to support treatment decisions for each patient.