Abstract Background and Hypothesis Stress sensitivity may represent an important target for resilience-promoting, preventive interventions. Resilience Training (RT) is a 4-session, group-based behavioral intervention, focusing on mindfulness-based skills, that leads to reductions in psychopathology. To investigate the mechanisms of RT, the current study tested whether acquiring the skills taught in RT leads to decreases in psychopathology via reductions in one manifestation of stress sensitivity, emotion reactivity, and associated changes in hippocampal-frontal connectivity. Study Design An open trial of RT was conducted in 103 non-help-seeking young adults with mild-to-moderate psychotic experiences (PEs) and/or symptoms of depression. Transdiagnostic symptoms, emotion reactivity, and mindfulness-related skills were measured, and, in a subset of participants (n = 41), resting-state, functional magnetic resonance imaging (fMRI) data were collected, before and after completion of RT. Study Results Replicating and extending findings of prior studies of RT, significant increases in mindfulness-related RT skills and significant decreases in transdiagnostic symptoms and emotion reactivity, as well as changes in hippocampal-frontal functional connectivity, were observed following RT (all P < .02). Mediation analyses revealed that associations between the acquisition of the RT skills and decreases in symptoms (P < .006) were fully mediated by the decrease in emotion reactivity, which was also correlated with a significant pre-to-post increase in hippocampal-dorsolateral prefrontal cortex connectivity (P = .032). Conclusions RT may lead to improvements in mental health by increasing the capacity to manage day-to-day stress. Future randomized controlled trials with extended follow-up can determine whether such improvements decrease the likelihood of developing disabling mental illnesses in transdiagnostically at-risk individuals. <<<