In 1825, Johann Friedrich Engelhart discovered that the ratio of iron to protein is identical in the hemoglobins of several species. From the known atomic mass of iron, he calculated the molecular mass of hemoglobin to n × 16000 (n = number of iron atoms per hemoglobin molecule, now known to be 4), the first determination of a proteins molecular mass. This "hasty conclusion" drew ridicule from colleagues who could not believe that any molecule could be so large. However, Gilbert Smithson Adair confirmed Engelharts results in 1925 by measuring the osmotic pressure of hemoglobin solutions.
Although blood had been known to carry oxygen since at least 1794, the oxygen-carrying property of hemoglobin was described by Hünefeld in 1840. In 1851, German physiologist Otto Funke published a series of articles in which he described growing hemoglobin crystals by successively diluting red blood cells with a solvent such as pure water, alcohol or ether, followed by slow evaporation of the solvent from the resulting protein solution. Hemoglobin's reversible oxygenation was described a few years later by Felix Hoppe-Seyler.
With the development of X-ray crystallography, it became possible to sequence protein structures. In 1959, Max Perutz determined the molecular structure of hemoglobin. For this work he shared  the 1962 Nobel Prize in Chemistry with John Kendrew, who sequenced the globular protein myoglobin.
The role of hemoglobin in the blood was elucidated by French physiologist Claude Bernard.
The name hemoglobin is derived from the words heme and globin, reflecting the fact that each subunit of hemoglobin is a globular protein with an embedded heme group. Each heme group contains one iron atom, that can bind one oxygen molecule through ion-induced dipole forces. The most common type of hemoglobin in mammals contains four such subunits.