During the 1890s Smith began to offer his students at Penn a course of lectures on the history of chemistry, probably among the first such courses offered at an American university. His typed lecture notes, reflecting his view that chemistry's past reveals its rich culture and its humanism, are preserved in the Smith Collection.

A proven administrator, Smith was named vice provost of the university in 1898, then provost (at that time the chief executive officer) in 1911. Over the next decade, he presided over Penn's transformation into a major research institution. Despite his demanding administrative schedule, he still cultivated his long-standing interest in the history of chemistry. Smith's major works in the field — Chemistry in America (1914), The Life of Robert Hare (1917), James Woodhouse (1918), and Priestley in America (1920) — were all completed during his tenure as provost. He also maintained an active public life, serving on the U.S. Assay Commission, and the Electoral College and the Commission for Revision of the Constitution of Pennsylvania. He retired from the university in 1920 and devoted the last eight years of his career to pursuing historical research on American chemistry and advancing its cause. Twice again president of the American Chemical Society — in 1921 and 1922 — he was instrumental in founding the society's Divisions of Chemical Education and of the History of Chemistry. Through his collecting, his institutional activities, and his publications, Edgar Fahs Smith helped to create the history of chemistry in the United States. He died in Philadelphia on May 3, 1928.