Flexner was born in Louisville, Kentucky on November 13, 1866. He was the sixth of nine children born to German Jewish immigrants, Ester and Moritz Flexner. He was the first in his family to complete high school and go on to college. In 1886, at age 19, Flexner completed a B.A. in classics at Johns Hopkins University, where he studied for only two years. In 1905, he pursued graduate studies in psychology at Harvard University, and at the University of Berlin. He did not, however, complete work on an advanced degree at either institution.

In 1896, Flexner married a former student of his school, Anne Laziere Crawford. She was a teacher who soon became a successful playwright and children’s author. The success of her play Mrs. Wiggs of the Cabbage Patch (based on the 1901 novel) funded Flexner’s studies at Harvard and his year abroad at European universities. The couple had two daughters Jean and Eleanor. Jean went on to become one of the original employees of the United States Division of Labor Standards. Eleanor Flexner became an independent scholar and pioneer of women’s studies.

In 1908, Flexner published his first book, The American College. Strongly critical of many aspects of American higher education, it denounced, in particular, the university lecture as a method of instruction. According to Flexner, lectures enabled colleges to “handle cheaply by wholesale a large body of students that would be otherwise unmanageable and thus give the lecturer time for research.” In addition, Flexner was concerned about the chaotic condition of the undergraduate curriculum and the influence of the research culture of the university. Neither contributed to the mission of the college to address the whole person. He feared that “research had largely appropriated the resources of the college, substituting the methods and interest of highly specialized investigation for the larger objects of college teaching.”

His book attracted the attention of Henry Pritchett, president of the Carnegie Foundation, who was looking for someone to lead a series of studies of professional education. The book consistently cited Pritchett in discussions of views on educational reform, and the two soon arranged to meet through the then-president of Johns Hopkins University, Ira Remsen. Although Flexner had never set foot inside a medical school, he was Pritchett’s first choice to lead a study of American medical education, and soon joined the research staff at the Carnegie Foundation in 1908. Although not a physician himself, Flexner was selected by Pritchett for his writing ability and his disdain for traditional education.

In 1910, Flexner published the Flexner Report, which examined the state of American medical education and led to far-reaching reform in the training of doctors. The Flexner Report led to the closure of most rural medical schools and all but two African-American medical colleges in the United States, given his adherence to germ theory, in which he argued that if not properly trained and treated, African-Americans and the poor posed a health threat to middle/upper class European-Americans. His position was:

Between 1912 and 1925, Flexner served on the Rockefeller Foundation’s General Education Board, and after 1917 was its secretary. With the help of the board, he founded another experimental school, the Lincoln School, which opened in 1917, in cooperation with the faculty at Teachers College of Columbia University.

The Bambergers, heirs to a department store fortune, were set on creating a medical school in Newark, New Jersey that gave admissions preference to Jewish applicants in an effort to fight the rampant prejudice against Jews in the medical profession at that time. Flexner informed them that a teaching hospital and other faculties required a successful school. A few months later, in June 1930, he had persuaded the Bamberger siblings and their representatives to fund instead the development of an Institute for Advanced Study.

In his 1930 Universities: American, English, German, Flexner returned to his earlier interest in the direction and purpose of the American university, attacking distractions from serious learning, such as intercollegiate athletics, student government, and other student activities.

During his time there, Flexner helped bring over many European scientists who would likely have suffered persecution by the rising Nazi government. This included Albert Einstein, who arrived at the Institute in 1933 under Flexner’s directorship.

Flexner died in Falls Church, Virginia, in 1959 at 92 years of age. He was buried in Cave Hill Cemetery in Louisville, Kentucky.