Ayahuasca, a plant-based hallucinogen that serves as a spiritual medicine in South America, has improved depression in at least one placebo-controlled clinical trial. Case studies suggest that dramatic behavioral changes often follow the Ayahuasca ceremony, but most explanations of antidepressant effects focus on changes in mindfulness. This study investigated whether both mindfulness and behavioral activation might contribute to these anti-depressant effects. We surveyed individuals (N = 152) about their changes in depressive symptoms, behavioral activation, and mindfulness after an Ayahuasca experience. Mindfulness was strongly associated with reduced depression severity (<i>r </i>= - .670, <i>p </i>< .001), while behavioral activation was moderately linked (<i>r </i>= - .474, <i>p </i>< .001). Changes in depressive symptoms (Center for Epidemiological Sciences Depression Short Form [CES-D-10]) covaried with subscales from the Five Facet Mindfulness Questionnaire [FFMQ] and Experiences Questionnaire [EQ], confirming previous findings (β = -.57, 95% CI -5.70, -3.25), <i>p </i>< .001). In addition, a modification of the Behavioral Activation for Depression Scale-Short Form [BADS-SF] accounted for significant unique variance in the improvements in depression (β = - .16, 95% CI -6.32, -0.08), <i>p </i>< .05). Changes in behavioral activation likely serve as a mechanism underlying Ayahuasca's antidepressant effects. Future clinical trials could benefit from tracking behavioral activation.