He was involved primarily with cuneiform, particularly discoveries in Uruk, and with the Sumerians and their language.
From 1930 onward, Falkenstein taught as a professor of Assyriology at the Göttingen University.
In 1940 he accepted a teaching assignment at Heidelberg University as a professor of semitic languages.
In 1941 he flew to Baghdad with Fritz Grobba when Haj Amin al-Husseini and Rashid Ali al-Gaylani organized a brief, pro-German coup supported by weapons shipments from the German Reich.
From 1939 to 1944 he was editor of the professional journal "Orientalische Literaturzeitung"; from 1950 until his death in 1966 he edited the "Zeitschrift für Assyriologie".