Background The significant heterogeneity of elderly AML patients’ biological features has caused stratification difficulties and adverse prognosis. This paper did a correlation study between their genetic mutations, clinical features, and prognosis to further stratify them. Methods 90 newly diagnosed elderly acute myeloid leukemia (AML) patients (aged ≥60 years) who detected genetic mutations by next-generation sequencing (NGS) were enrolled between April 2015 and March 2021 in our medical center. Results A total of 29 genetic mutations were identified in 82 patients among 90 cases with a frequency of 91.1%. DNMT3A, BCOR, U2AF1, and BCORL1 mutations were unevenly distributed among different FAB classifications ( p < 0.05). DNMT3A, IDH2, NPM1, FLT3-ITD, ASXL1, IDH1, SRSF2, BCOR, NRAS, RUNX1, U2AF1, MPO, and WT1 mutations were distributed differently when an immunophenotype was expressed or not expressed ( p <0.05). NPM1 and FLT3-ITD had higher mutation frequencies in patients with normal chromosome karyotypes than abnormal chromosome karyotypes ( p <0.001, p =0.005). DNMT3A and NRAS mutations predicted lower CR rates. DNMT3A, TP53, and U2AF1 mutations were related to unfavorable OS. TET2 mutation with CD123+, CD11b+ or CD34- predicted lower CR rate. IDH2+/CD34- predicted lower CR rate. ASXL1+/CD38+ and SRSF2+/CD123- predicted shorter OS. Conclusion The study showed specific correlations between elderly AML patients’ genetic mutations and clinical features, some of which may impact prognosis.