Brief, school-based mental health interventions hold promise for reducing barriers to mental health support access, a critical endeavor in light of increasing rates of mental health concerns among youth. However, there is no consensus on whether or not brief school-based interventions are effective at reducing mental health concerns or improving wellbeing. This systematic review and meta-analysis aims to provide consensus and determine directions for future work. Articles were included if they examined a brief (≤ four sessions or 240 minutes of intervention time) psychosocial intervention, were conducted within a Pre-K through 12th-grade school setting, included at least one treatment outcome evaluating mental health or wellbeing, and were published since 2000. A total of 2767 papers were identified through database searching, of which 53 papers (k studies = 48) were ultimately selected for inclusion. A total of 22,532 students were included across studies and a total of 48 unique interventions were examined. A total of 189 effect sizes were extracted. On average, interventions led to statistically significant improvements in mental health/wellbeing outcomes versus control conditions up to one month (g = .17, p = .04), six months (g = .22, p = .002), and one year (g = .18, p = .005) post-intervention. There may be benefits to brief school-based interventions from a preventative public-health standpoint; future research may focus on how to optimize their real-world utility. Prospero preregistration: CRD42021255079.