Purpose This study assessed variation in childhood cancer survival by Indigenous status in Australia, and explored the effect of place of residence and socio-economic disadvantage on survival. Methods All children diagnosed with cancer during 1997-2007 were identified through the Australian Pediatric Cancer Registry. Cox regression analysis was used to assess the adjusted differences in survival. Results Overall, 5-years survival was 75.0 % for Indigenous children (n = 196) and 82.3 % for non-Indigenous children (n = 6,376, p = 0.008). Compared to other children, Indigenous cases had 1.36 times the risk of dying within 5 years of diagnosis after adjustments for rurality of residence, socio-economic disadvantage, cancer diagnostic group, and year of diagnosis (95 % CI 1.01-1.82). No significant survival differential was found for leukemias or tumors of the central nervous system; Indigenous children were 1.83 times more likely (95 % CI 1.22-2.74) than other children to die within 5 years from 'other tumors' (e.g., lymphomas, neuroblastoma). Among children who lived in 'remote/very remote/outer regional' areas, and among children with a subgroup of 'other tumors' that were staged, being Indigenous significantly increased the likelihood of death (HR = 1.69, 95 % CI 1.10-2.59 and HR = 2.99, 95 % CI 1.35-6.62, respectively); no significant differences by Indigenous status were seen among children with stage data missing. Conclusions Differences in place of residence, socio-economic disadvantage, and cancer diagnostic group only partially explain the survival disadvantage of Indigenous children. Other reasons underlying the disparities in childhood cancer outcomes by Indigenous status are yet to be determined, but may involve factors such as differences in treatment.