BACKGROUND: There is a paucity of data on the burden of heart failure (HF) in Central Australia, the most populous Indigenous region in the country. AIMS: To characterize Indigenous and non-Indigenous Australians with HF in Central Australia. METHODS: Consecutive patients with HF and reduced ejection fraction <50% were included for the period 2019 to 2021. Clinical, echocardiographic and major adverse cardiovascular events (MACE) data were collected. RESULTS: Four hundred twenty-four patients with HF were included (70% Indigenous, 59% male; follow-up 2.2 ± 0.5 years). Indigenous Australians were younger (53 ± 15 vs 68 ± 13 years, P < 0.001) with higher rates of rheumatic heart disease (18% vs 1%, P < 0.001), diabetes (63% vs 33%, P < 0.001) and severe chronic kidney disease (CKD; 32% vs 7%, P < 0.001). HF was more prevalent among Indigenous (138 [95% confidence interval (CI), 123-155] per 10 000) compared with non-Indigenous Australians (53 [95% CI, 44-63] per 10 000), particularly among younger individuals and females. There were similar HF aetiologies between groups. Guideline-directed medical therapy (GDMT) was suboptimal and similar between the groups: angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (64% vs 67%, P = 0.47) and β-blockers (68% vs 71%, P = 0.47). Indigenous Australians had a significantly higher rate of MACE (54% vs 28%, P < 0.001) and death from any cause (24% vs 13%, P = 0.013). CONCLUSIONS: HF is more than two times as prevalent among Indigenous Central Australians, particularly among younger individuals and females. Despite similar HF aetiologies and GDMT, MACE and mortality outcomes are higher in Indigenous individuals with HF. These data have implications for efforts to close the Indigenous gap in morbidity and mortality.