The Department of Near Eastern Studies had its origin in the Semitic Seminary, which dates back to the founding of the University in 1876. Since the study of semitics had traditionally been limited to theological seminaries, including such studies in a secular institution was a novel venture, so much so that an instructor could not be found initially. In 1876, when Thomas C. Murray, a graduate student, requested a fellowship at the University to study semitics he was appointed Associate instead. Murray remained the sole faculty member of the Semitic Seminary until his death in 1879.

In 1883, Paul Haupt (Ph.D. University of Leipzig, 1878) arrived from Germany to fill the newly established William W. Spence Chair of Semitic Languages. Haupt was a scholar of considerable renown, attracting students from the United States and Europe. Among the traditions he began was the suspension of all his classes for the month of January, during which time he conducted a month-long intensive course in Assyriology, attended by scholars from throughout the country. He continued this for the forty-three years he was a Hopkins faculty member. In 1896, under his direction, the department became the Oriental Seminary.

Many of Haupt's students came to Hopkins to work with him; one of these was Cyrus Adler, who received from Hopkins, in 1897, the first Ph.D. ever given in Semitics in the United States. Adler remained a faculty member for six years before leaving in 1893 to become librarian of the Smithsonian Institute. Another former student, Rabbi William Rosenau (Ph.D. Johns Hopkins University, 1900), joined the faculty in 1900 as an assistant professor. Rosenau served as associate professor from 1925 until 1932, when he retired and was named Professor Emeritus.

The faculty under Haupt was quite small, and, upon his death in 1926, there was no full professor in the Seminary until the appointment of William Foxwell Albright (A.B. Upper Iowa University, 1912; Ph.D. Johns Hopkins University, 1916) to the W. W. Spence Chair in 1929. Albright was a world-class scholar who wrote over eight hundred books, articles, and pamphlets. He knew some twenty-five languages, co-authored the Anchor Bible (1956-1971), was the second archaeologist and ancient historian to be elected to the National Academy of Sciences (1955) and was the recipient of twenty-nine honorary degrees. Under his guidance, the Oriental Seminary thrived, with emphasis being placed on graduate studies, although undergraduate courses were offered as well.

After Albright's retirement in 1958 the Spence Chair remained empty for thirteen years, while University officials searched for someone of Albright's eminence to fill the Chair. In 1971, Delbert R. Hillers (B.A., B.D. Concordia Seminary, 1954, 1957; M.A., Ph.D. Johns Hopkins University, 1958, 1963) was appointed to fill the Spence Chair. Hillers, a specialist in Old Testament Studies, was appointed to head the newly renamed Department of Near Eastern Studies in 1964. Hans Goedicke (Ph.D. University of Vienna, 1949), an Egyptologist, was named to the faculty in 1962 and became Professor in 1968; in 1971 he succeeded Hillers as chair of the department. Georg Krotkoff (Ph.D. University of Vienna, 1950) held the chair from 1973 to 1976, at which time Hillers resumed leadership of the department. Hillers was again succeeded, in 1980, by Goedicke. In 1984 Jerrold S. Cooper was appointed to chair the department, and was succeeded in 1991 by P. Kyle McCarter, Jr.