Extensive research on traumatic life experiences reveals how healthy development can be derailed and brain architecture altered by excessive or prolonged activation of the body’s stress response, impacting health, mental health, learning, behavior and relationships. Schools offer a unique environment to prevent and counter the impacts of childhood trauma. This study aimed to investigate empirical evidence for school-wide trauma-informed approaches that met at least two of the three essential elements of trauma-informed systems defined by SAMSHA (2014). SAMHSA’s concept of trauma and guidance for a trauma-informed approach. HHS Publication No. (SMA) 14-4884. Rockville: Substance Abuse and Mental Health Services Administration. https://store.samhsa.gov/shin/content/SMA14-4884.pdf) and consider commonalities in approaches, drivers of change, challenges and learnings related to implementation, sustainability and outcomes for students. A systematic review searching foremost databases was conducted for evidence of trauma-informed school-wide approaches used between 2008 and 2019. Four papers were identified, incorporating four school-wide approaches, The Healthy Environments and Response to Trauma in Schools (HEARTS) Model; The Heart of Teaching and Learning (HTL): Compassion, Resiliency, and Academic Success Model; The New Haven Trauma Coalition (NHTC) and The Trust-Based Relational Intervention. Although heterogeneous, the models shared core elements of trauma-informed staff training, organization-level changes and practice change, with most models utilizing student trauma-screening. Generalizability of the findings was low given the small number of studies, the mix of mainstream and specialist schools and high risk of bias. Given the limitations of research in this emergent but rapidly accelerating field, future research is urgently required to understand the interaction between core elements of a trauma-informed approach, teaching pedagogy and organizational factors that support the embedding, use and transferability of school-wide approaches.