Social-emotional skills are essential for preschool children's mental health and later school success. Considering the variety of school-based interventions aiming to target SEL development, it remains unclear what programs can be considered evidence-based, and what features characterize well-established programs. Hence, the current systematic review aimed (1) to classify classroom-wide SEL programs according to the criteria for evidence-based interventions; (2) to synthesize studies of programs categorized as well-established; and (3) to analyze study-level and overall risk of bias. Interventions were assessed for inclusion, and corresponding studies were systematically searched. A total of 81 studies corresponding to 38 programs were identified, and 24 studies corresponding to four programs classified as well-established were further analyzed. The results indicated that (1) a limited number of classroom-wide interventions (10.5%) meet the criteria for well-established interventions; (2) program implementation is associated with significant improvement in social-emotional competence, reduced risk of emotional, and behavioral problems, as well as with emerging evidence of positive effects on executive functions or school readiness; and (3) outcomes are reported in the context of mainly rigorously conducted experimental research, which could explain the low risk bias ratings for random assignment, baseline equivalence, or attrition. Taken together, these findings suggest that well-established classroom-based interventions could be promoted as examples of best practices which can be systematically implemented within schools. However, more research is needed to identify key ingredients of program effectiveness, as well as to understand the contextual school-related factors, which enable successful transfer from research to large-scale implementation of classroom-wide SEL practices.