The first published description of a case of leukemia in medical literature dates to 1827, when French physician Alfred-Armand-Louis-Marie Velpeau described a 63-year-old florist who developed an illness characterized by fever, weakness, urinary stones, and substantial enlargement of the liver and spleen.

Velpeau noted that the blood of this patient had a consistency "like gruel", and speculated that the appearance of the blood was due to white corpuscles.

In 1845, a series of patients who died with enlarged spleens and changes in the "colors and consistencies of their blood" was reported by the Edinburgh-based pathologist J.H. Bennett; he used the term "leucocythemia" to describe this pathological condition.
 

The term "leukemia" was coined by Rudolf Virchow, the renowned German pathologist, in 1856. As a pioneer in the use of the light microscope in pathology, Virchow was the first to describe the abnormal excess of white blood cells in patients with the clinical syndrome described by Velpeau and Bennett.

As Virchow was uncertain of the cause of the white blood cell excess, he used the purely descriptive term "leukemia" (Greek: "white blood") to refer to the condition.

Further advances in the understanding of acute myeloid leukemia occurred rapidly with the development of new technology.

In 1877, Paul Ehrlich developed a technique of staining blood films which allowed him to describe in detail normal and abnormal white blood cells.

Wilhelm Ebstein introduced the term ''"acute leukemia"'' in 1889 to differentiate rapidly progressive and fatal leukemias from the more indolent chronic leukemias. The term "myeloid" was coined by Neumann in 1869, as he was the first to recognize that white blood cells were made in the bone marrow (Greek: µυєλός, ''myelos'' = (bone) marrow) as opposed to the spleen.

The technique of bone marrow examination to diagnose leukemia was first described in 1879 by Mosler. Finally, in 1900 the myeloblast, which is the malignant cell in AML, was characterized by Naegeli, who divided the leukemias into ''myeloid'' and ''lymphocytic''.

In 2008, AML became the first cancer genome to be fully sequenced. DNA extracted from leukemic cells were compared to unaffected skin. The leukemic cells contained acquired mutations in several genes that had not previously been associated with the disease.