Major Depressive Disorder (MDD) manifests in 20–30% of college students, with increased incidence in recent decades. Very limited research has assessed the efficacy of evidence-based interventions for MDD in college students. Mindfulness-Based Therapy (MBT) and Behavioral Activation (BA) are two interventions with significant potential to meet demands of college counseling clinics and effectively treat college students with MDD. This study utilized a randomized controlled research design (n = 50) to examine the efficacy of four-sessions of abbreviated MBT and BA relative to a wait-list control condition with depressed college students. Intent-to-treat data analyses on depression outcome measures suggested both treatments were superior to the control group. There were significant pre-post treatment improvements across measures of depression, rumination, stress, and mindfulness, gains largely maintained at 1-month follow-up. Neither active treatment effectively reduced somatic anxiety. Both treatments generally had moderate-strong effect sizes relative to the control group, and based on depression response and remission criteria, 56–79% of patients exhibited clinically significant improvement. Based on reliable change indices, 75–85% experienced clinically significant reductions in depression. There was strong therapist competence and adherence to treatment protocols and high patient satisfaction with both interventions. Study limitations and implications for the assessment and treatment of depressed college students are discussed.