Psychotherapy research has long preferred explanatory over predictive models. As a result, psychotherapy research is currently limited in the variability that can be accounted for in the process and outcome of treatment. The present study is a proof-of-concept approach to psychotherapy science that uses a data-driven approach to achieve robust predictions of the process and outcome of treatment. A trial including 65 therapeutic dyads was designed to enable an adequate level of variability in therapist characteristics, overcoming the common problem of restricted range. A mixed-model, data-driven approach with cross-validation machine learning algorithms was used to predict treatment outcome and alliance (within- and between-clients; client- and therapist-rated alliance). Based on baseline predictors only, the models explained 52.8% of the variance for out-of-sample prediction in treatment outcome, and 24.1-52.8% in therapeutic alliance. The identified predictors were consistent with previous findings and point to directions for future investigation. Although limited by its sample size, this study serves as proof of the great potential of the presented approach to produce robust predictions regarding the process and outcome of treatment, offering a potential solution to problems such as p-hacking and lack of replicability. Findings should be replicated using larger samples and distinct populations and settings.