Born in Erlangen, he studied in Leipzig and Berlin, gaining his habilitation in 1874 as a lecturer of Semitic languages and Assyriology in Leipzig. In 1885 he became a full professor at Leipzig, afterwards serving as a professor at the Universities of Breslau (1893) and Berlin (1899).
He was co-founder of the Deutschen Orientgesellschaft (German Oriental Society) and director of the Vorderasiatischen Abteilung (Near Eastern Department) of the Royal Museums.
Friedrich Delitzsch specialized in the study of ancient Middle Eastern languages, and published numerous works on Assyrian language, history and culture. He is remembered today for his scholarly critique of the Old Testament. In a 1902 controversial lecture titled "Babel and Bible", Delitzsch maintained that many Old Testament writings were borrowed from ancient Babylonian tales, including the stories of the Creation and Flood from the Book of Genesis. During the following years there were several translations and modified versions of the "Babel and Bible". In the early 1920s, Delitzsch published the two-part Die große Täuschung (The Great Deception), which was a critical treatise on the book of Psalms, prophets of the Old Testament, the invasion of Canaan, etc. Delitzsch also stridently questioned the historical accuracy of the Hebrew Bible and placed great emphasis on its numerous examples of immorality (see also Julius Wellhausen).
Although Delitszch's proposal to replace the Old Testament with German myths did not extend to this revision, his student Paul Haupt was one of the major advocates of the thesis of the Aryan Jesus.