Although liberal arts education had been offered since the university's founding in 1847, the College of Liberal Arts came into existence only at the dawn of the new century.

In 1900–01, the University of Iowa reorganized around an innovative structure called "the college." Within the university, colleges were established to nurture disciplinary areas (later formalized as departments) that were responsible for teaching and scholarship in specific subject areas. 

George MacLean, president of the university from 1899 to 1911, "deserves to be called the father of the modern University of Iowa," according to Stow Persons, emeritus professor of history and author of The University of Iowa in the Twentieth Century: An Institutional History. When MacLean arrived on campus, the administrative structure in place included six "departments" (Collegiate, Law, Medical, Homeopathic Medical, Dental, and Pharmacy) with a hospital attached to the medical departments. The Collegiate Department, by far the largest unit of the university in 1899, was the precursor of the modern College of Liberal Arts. It offered undergraduate and graduate work, with four courses of study: classical, philosophical, general scientific, and engineering. Within each course of study, the student took prescribed courses in the freshman and sophomore years and electives in the upperclass years.

President MacLean introduced a new academic structure to the University of Iowa that has been remarkably stable for the past century. The Collegiate Department became the College of Liberal Arts, one of seven colleges established in 1900–01, along with the Graduate College and five professional colleges. Eventually, other colleges evolved from Liberal Arts: Engineering in 1905, Education in 1913, and Commerce (now Business) in 1921.

In the academic year 1904–05, the nineteenth-century "courses of study" were replaced by the departmental major, which still survives. Students were, according to the university bulletin for that year, required to undertake "a major study in some one department, extending through the [junior and senior] years." The first year and part of the sophomore year were devoted to general education courses, and all students were required to take courses in English, foreign language, social sciences, and natural sciences and mathematics. The General Education program, completed by all students in the College, still includes courses in all these areas.

"It would be hard to overestimate the general significance of the new organization for the College of Liberal Arts," Persons writes. From the areas of instruction that existed in 1900, most consisting of a single professor, semi-autonomous academic departments gradually emerged. The deans controlled budgets and had a say in faculty appointments, but the substance of what was taught and the research undertaken was under the control of the departments. A new university official emerged, the head of department, who could exercise extraordinary power to shape the department and determine its academic standing. The heads were appointed by the dean but served indefinitely, some for decades: Seashore in psychology and philosophy; Shambaugh in political science; Calvin in geology; Macbride in botany; Stewart and Van Allen in physics; Schlesinger in history; and Mabie in speech. These department heads had a tremendous hand in making the College of Liberal Arts what it is today.

The college changed its name to the College of Liberal Arts and Sciences in 2001.

Founding faculty of the college (1900-1901)

In 1900–01, "departments," as we know them today, did not yet exist, nor did the departmental "major." The University Bulletin for 1900–01 lists professors in 19 disciplinary areas—one professor per area, except in Greek, where there were two professors. Some areas had assistant professors, bringing the professorial faculty to 28, two of whom were women.

These faculty are listed in the order that their areas of instruction and courses were listed in the 1900–01 Bulletin. Three of these individuals served as dean of the College, and five campus buildings bear the names of faculty listed here: