There is a high prevalence of heart failure (HF) in the general population, but it is more common in black people. We evaluated the association between genomic ancestry and mitochondrial haplogroups (mt-haplogroups) with HF etiology in 503 Brazilian patients. We elicited Mt-haplogroups by analyzing the control region of mitochondrial DNA, and genomic ancestry, by using 48 autosomal insertion-deletion ancestry informative markers. Hypertensive (28.6%, n = 144) and ischemic (28.4%, n = 143) etiologies of HF were the most prevalent herein. Our results showed that 233 individuals (46.3%) presented African mitochondrial (mt)-haplogroups, and the major contribution in the genomic ancestry analysis was the European ancestry (57.5% (±22.1%)). African mt-haplogroups were positively associated with a diagnosis of hypertensive cardiomyopathy (odds ratio, OR 1.55, confidence interval, CI 95% 1.04–2.44, P = 0.04) when compared with European mt-haplogroups. Regarding the genomic ancestry, the African ancestry variant had higher risks (OR 7.84, 95% CI 2.81–21.91, P<0.001), whereas the European ancestry variant had lower risks (OR 0.14, 95% CI 0.04–5.00, P<0.001) for developing the hypertensive etiology. In addition, European ancestry showed an OR of 4.05 (CI 95% 1.53–10.74, P = 0.005), whereas African ancestry showed an OR of 0.17 (CI 95% 0.06–0.48, P = 0.001) for developing ischemic etiology. In conclusion, this study supports the importance of using ancestry informative markers and mitochondrial DNA to study the genetics of complex diseases in admixed populations to improve the management, treatment and prevention of these illnesses. Therefore, the ancestry informative markers and mt-haplogroups could provide new biomarkers to be associated with HF etiologies and be used as a premise for more specific management.