Objective: To compare disease presentation and outcome in Aboriginal and non-Aboriginal children with acute leukaemia and to assess the impact of remoteness and area-based socioeconomic disadvantage. Design: A retrospective review of children treated for acute leukaemia from South Australia (SA), Northern Territory (NT) and Western Australia (WA) between 2009 and 2018. Setting: Women’s and Children’s Hospital (WCH), Adelaide and Perth Children’s Hospital (PCH) - the sole referral sites for paediatric cancer for SA, NT and WA. Participants: Eligible patients, aged between 1 day and <18 years, diagnosed with acute leukaemia. Main Outcome Measures: Leukaemia diagnosis and overall survival. Results: Analysis of 455 children treated for acute leukaemia showed inferior survival outcomes were associated with remote/very remote localities (p=0.004). Five-year overall survival was 91.7% (95% CI: 87.9%-94.3%) for children with ALL and 69.8% (56.7%-79.5%) for AML. A large percentage of Aboriginal children from SA/NT were diagnosed with AML compared to others (60.0% vs. 14.4%, p=0.001). A trend towards inferior overall survival was seen for Aboriginal children with ALL compared to non-Aboriginal children (82.4% vs. 92.2%, p=0.07) and 55.6% were high-risk by study criteria; however, MRD testing did not identify any high MRD cases. Aboriginal children were less likely to be enrolled on clinical trials (34.5% vs. 53.1%, p=0.03) and more likely to be lost to follow-up (41.4% vs. 13.2%, p<0.001). Conclusion: Aboriginal ethnicity and geographic remoteness of residence are adverse prognostic factors for Australian children with leukaemia. Additional strategies are required to ensure improvements in follow-up and survival of these children.