KleinSmid started his academic career at DePauw University where he was a Professor of Education and Psychology. He became University of Southern California"s fifth president in 1921. A high priority of his administration was to expand professional training programs, and President von KleinSmid also presided over a building program that added nine major structures to the university campus.
With the onset of the Great Depression at decade’s end, University of Southern California was forced to retrench in the 1930s.
During World World War II (1939–1945), army barracks were constructed on campus, and the curriculum reflected a wartime emphasis on international relations, history, geography, languages, science and the like. Some 2,000 military trainees added to crowded conditions on campus.
After the war, the lack of space at University of Southern California grew even worse, as the G.I. Bill brought former servicemen to the university for study. Enrollment soared from 8,500 in 1945 to more than 24,000 in 1947.
In 1946 KleinSmid, then aged 70, elected to step down and became University of Southern California"s chancellor, a position he held for the remaining nine years of his life.
He was recognized as "one of three of the nation"s most distinguished citizens" through the National Institute of. The Swiss-born American artist Adolfo Müller-Ury (1862–1947) painted his three-quarter length portrait in 1931. lieutenant was the gift of the Doheny family to the University of Southern California, who de-accessioned it in the 1980s.
KleinSmid was a skilled fencer, and helped found the University of Southern California Fencing Club.
A passionate supporter of eugenics, which he described as "the science of good birth", and related sterilization programs, KleinSmid co-founded the Human Betterment Association. He argued that "The acceptance is even now upon us, and the application of the principles of Eugenics to organized society is one of the most important duties of the social scientist of the present generation." KleinSmid died on July 9, 1964.