Intervention scientists have proposed a focus on empirically supported principles of change (ESPCs) in psychotherapies. We explored this proposition as applied to youth psychotherapies, focusing on five candidate ESPCs—calming, increasing motivation, changing unhelpful thoughts, solving problems, and practicing positive opposites. We synthesized 348 treatment–control comparisons from 263 randomized controlled trials (RCTs) spanning six decades, testing treatments for anxiety, depression, attention-deficit/hyperactivity disorder, and conduct problems. We found that ESPCs could be reliably identified and distinguished by independent coders and that psychotherapies most often included fewer than three ESPCs. However, across the entire study pool and the anxiety subsample, when we controlled for dose, treatments with all five ESPCs showed effects about twice as large as treatments with fewer ESPCs. The findings suggest that ESPCs are reliably identifiable, that they are associated with variations in treatment effect size, and that treatments containing more ESPCs may produce greater therapeutic benefit.