Psychological flexibility refers to a modifiable pattern of interacting with one’s experiences with openness and awareness (acceptance-and-mindfulness) and active engagement guided by personal values (commitment-and-behavioral activation). Psychological flexibility has a base of research literature that supports its utility as a model of human behavioral health and pathology. Although the model is central in organizing the therapeutic processes of Acceptance and Commitment Therapy, researchers have argued that psychological flexibility processes might be activated in other effective therapy models included in routine psychotherapy, even if those models do not purport to target those processes. This study explored the degree to which aspects of clients’ psychological flexibility, specifically acceptance-and-mindfulness and commitment-and-behavioral activation, changed after episodes of routine psychotherapy and were predictors of outcome changes for a clinically heterogeneous sample (n = 197) in a naturalistic treatment setting. Results showed statistically significant and small improvements in acceptance-and-mindfulness (d = 0.22) and commitment-and-behavioral activation (d = 0.24) and that changes in psychological flexibility were significant predictors of changes in both flourishing and distress, explaining 42% and 23% of those respective therapy outcomes. Whereas a mix of therapy approaches may slightly improve psychological flexibility, more explicit attention to strengthening it might benefit the work of diverse psychotherapists given its potential relevance to achieving common overarching therapy outcomes.