Importance: Social-emotional competence in early childhood influences long-term mental health and well-being. Interest in the potential to improve child health and educational outcomes through social and emotional learning (SEL) programs in early childhood education and care (ECEC) settings is increasing. Objective: To conduct a systematic review and meta-analysis of studies examining the social, emotional, and early learning outcomes associated with universal curriculum-based SEL programs delivered to children aged 2 to 6 years in center-based ECEC settings. Data Sources: Keyword searches of Education Resources Information Center (ERIC), MEDLINE Complete, PsycINFO, and Proquest Dissertations and Theses Global databases were conducted to identify all relevant studies published from January 1, 1995, through December 31, 2017. Study Selection: Studies included in this review examined universal curriculum-based SEL intervention delivered to children aged 2 to 6 years in a center-based ECEC setting. All assessed individual-level social and/or emotional skill after the SEL intervention and used an experimental or quasi-experimental design (ie, studies that did not or were not able to randomly allocate participants to intervention and control groups) with a control group. Data Extraction and Synthesis: A total of 13 035 records were screened, of which 362 were identified for full-text review. A systematic literature review was conducted on 79 studies. Multilevel random-effects meta-analyses were conducted on 63 eligible studies from October 2 through 18, 2018. Main Outcomes and Measures: Social competence, emotional competence, behavioral self-regulation, behavior and emotional challenges, and early learning outcomes. Results: This review identified 79 unique experimental or quasi-experimental studies evaluating the effect of SEL interventions on preschooler outcomes, including a total of 18 292 unique participants. Sixty-three studies were included in this meta-analysis. Compared with control participants, children in intervention conditions showed significant improvement in social competence (Cohen d [SE], 0.30; [0.06]; 95% CI, 0.18-0.42; P < .001), emotional competence (Cohen d [SE], 0.54 [0.16]; 95% CI, 0.22-0.86; P < .001), behavioral self-regulation (Cohen d [SE], 0.28 [0.09]; 95% CI, 0.11-0.46; P < .001), and early learning skills (Cohen d [SE], 0.18 [0.08]; 95% CI, 0.02-0.33; P = .03) and reduced behavioral and emotional challenges (Cohen d [SE], 0.19 [0.04]; 95% CI, 0.11-0.28; P < .001). Several variables appeared to moderate program outcomes, including intervention leader, type of assessment, informant, child age, and study quality. Conclusions and Relevance: According to results of this study, social and emotional learning programs appeared to deliver at a relatively low intensity may be an effective way to increase social competence, emotional competence, behavioral self-regulation, and early learning outcomes and reduce behavioral and emotional difficulties in children aged 2 to 6 years. Social and emotional learning programs appear to be particularly successful at increasing emotional knowledge, understanding, and regulation.