Inclusion Criteria:

* Diagnosis of acute myeloid leukemia (AML) based on 2017 World Health Organization (WHO) criteria excluding acute promyelocytic leukemia with PML-RARA.

* Note: Patients with myeloid sarcoma without bone marrow involvement, acute leukemia of ambiguous lineage or blast transformation of chronic myelogenous leukemia (CML) are not eligible.
* No activating mutation in the Fms-like tyrosine kinase-3 (FLT3) defined as a ratio of mutant to wild-type allele \>= 0.05 by capillary electrophoresis or a variant allele fraction of \>= 5% by next generation sequencing from either bone marrow or peripheral blood.
* No evidence of central nervous system (CNS) involvement of AML.
* No prior chemotherapy for myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN) or AML including hypomethylating agents (e.g. azacitidine and decitabine), ruxolitinib or lenalidomide with the following exceptions:

* Emergency leukapheresis
* Hydroxyurea
* Growth factor/cytokine support
* All-trans retinoic acid (ATRA)
* Single dose of intrathecal cytarabine and/or methotrexate for patients undergoing lumbar puncture to evaluate for CNS involvement.
* Age \>= 60 years.
* Total bilirubin =\< 3 x upper limit of normal (ULN)
* Creatinine \< 3 x upper limit of normal (ULN) OR creatinine clearance \>= 30 mL/min/1.73m\^2