Landsteiner, the son of a prominent Viennese journalist, was educated at the University of Vienna, where he obtained his MD in 1891. After studying chemistry in Germany under Emil Fischer and in Switzerland under the German chemist Arthur Hantzsch, Landsteiner returned to the University of Vienna to work as a pathologist, serving as professor of pathology from 1911 to 1919. He then spent a couple of years in Holland before moving to America, where he took up an appointment with the Rockefeller Institute, New York, in 1922, remaining there until his death.

In 1902 Landsteiner announced one of the major medical discoveries of the century, that of the ABO blood group system. It was already known that the proteins in any animal or plant species were specific to that species and differed from those of other species, but Landsteiner went on to suggest that individuals within a species showed similar though small differences in their proteins. He knew that if serum (blood from which the cells and clotting factors have been removed) of one species is mixed with the erythrocytes (red cells) of another species the resulting mixture will agglutinate (clump together); he therefore decided to see what would happen when serum and erythrocytes from different humans were combined. In many cases there was no agglutination – it was as if the blood cells were mixed with their own serum – but in others he noted that agglutination occurred with just as strong an interaction as that between serum and cells of different species. The pattern of agglutination was such that Landsteiner proposed the existence of four distinct human blood groups, which he named A, B, AB, and O, based on the presence or absence in the blood of one or both of two antigens (substances against which antibodies react), which he named A and B. On this supposition individuals of blood group A (i.e., with antigen A) possess in their serum an antibody to antigen B, while group B individuals possess an antibody against antigen A; type AB individuals possess both antigens A and B (and therefore neither anti-A nor anti-B antibody), while type O individuals possess neither antigen and both antibodies.

Not only did Landsteiner's work at last permit successful blood transfusions and save many thousands of lives, it also raised profound questions about the nature of the immunological system – questions still being vigorously pursued. The ABO grouping was the first of many different groups to be discovered; Landsteiner himself, in 1927, discovered the second and third systems, the MN and the P. For his work on blood groups Landsteiner was awarded the 1930 Nobel Prize for physiology or medicine.

He also produced major results outside the field of serology, making (in 1908) one of the earliest breakthroughs in the conquest of polio. By taking pieces of the spinal cord of a polio victim and soaking them in liquid, he produced a mixture capable of infecting monkeys. Further work led him to conclude that a virus caused the disease. Landsteiner's approach permitted laboratory investigation and experimentation, which is the initial step in gaining understanding and control of any infective organism.

In the field of immunology Landsteiner demonstrated the specificity of antibodies by introducing the concept of the hapten. Haptens are small organic molecules that can stimulate antibody production only when combined with a protein molecule. Landsteiner combined haptens of known structures with such proteins as albumin and showed that small changes in the hapten would radically affect the production of antibodies.

Landsteiner was fortunate to be able to continue with creative scientific work virtually to the end of his life: he in fact suffered his fatal heart attack while working at his laboratory bench with a pipette in his hand. He was over 70 when, in 1940, he announced the discovery of the rhesus (Rh) factor, then responsible for the consequent serious illness or death of 1 in 200 white babies. The factor was so named as it was first detected in the blood of rhesus monkeys.

Landsteiner's work has continued to be the foundation for studies in many other related fields including that, for example, of the American biochemist William Boyd (1903– ). In his Genetics and the Races of Man (1950) Boyd demonstrated that analysis of blood samples allowed us to distinguish 13 races, namely, early European, northern and eastern European, Lapp, Mediterranean, African, Asian, Deavidian, Amerind, Indonesian, Melanesian, Polynesian and Australian aborigine.