Harvard College was established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony and was named for its first benefactor, John Harvard of Charlestown, a young minister who, upon his death in 1638, left his library and half his estate to the new institution. Harvard's first scholarship fund was created in 1643 with a gift from Ann Radcliffe, Lady Mowlson.

During its early years, the College offered a classic academic course based on the English university model but consistent with the prevailing Puritan philosophy of the first colonists. Although many of its early graduates became ministers in Puritan congregations throughout New England, the College was never formally affiliated with a specific religious denomination. An early brochure, published in 1643, justified the College's existence: "To advance Learning and perpetuate it to Posterity; dreading to leave an illiterate Ministry to the Churches."

The 1708 election of John Leverett, the first president who was not also a clergyman, marked a turning of the College toward intellectual independence from Puritanism. As the College grew in the 18th and 19th centuries, the curriculum was broadened, particularly in the sciences, and the College produced or attracted a long list of famous scholars, including Henry Wadsworth Longfellow, James Russell Lowell, William James, the elder Oliver Wendell Holmes, Louis Agassiz, and Gertrude Stein.

Charles W. Eliot, who served as president from 1869 to 1909, transformed the relatively small provincial institution into a modern university.

During his tenure, the Law and Medical schools were revitalized, and the graduate schools of Business, Dental Medicine, and Arts and Sciences were established. Enrollment rose from 1,000 to 3,000 students, the faculty grew from 49 to 278, and the endowment increased from $2.3 million to $22.5 million. It was under Eliot's watch that Radcliffe College was established. In the 1870s a group of women closely linked to Harvard faculty were exploring ways to make higher education more accessible to women.

One of this group, Stella S. Gilman, was married to historian and educator Arthur Gilman. In 1878, at the urging of his wife, Gilman proposed the foundation of a college for women to President Eliot. Eliot approved, and seven women were chosen to design the new institution. Among them were Stella Gilman, Alice Mary "Grave Alice" Longfellow, a daughter of the famous poet, and Elizabeth Cary Agassiz, the widow of renowned naturalist Louis Agassiz. In 1879, the "Harvard Annex" for women's instruction by Harvard faculty began operations. And in 1894 the Annex was chartered by the Commonwealth of Massachusetts as Radcliffe College, with Elizabeth Cary Agassiz as its first president.

Under Harvard President A. Lawrence Lowell (1909-33), the undergraduate course of study was redesigned to ensure students a liberal education through concentration in a single field with distribution of course requirements among other disciplines. Today, 51 fields of concentration are offered to Harvard College students. The tutorial system, also introduced by Lowell and still a distinctive feature of a Harvard education, offers undergraduates informal specialized instruction in their fields.

One of Lowell's most significant accomplishments was the House Plan, which provides undergraduates with a small-college atmosphere within the larger university. After being housed in or near Harvard Yard during freshman year, students go to one of 12 Houses in which to live for the remainder of their undergraduate careers. (A 13th House is designed for nonresident students.) Each House has a resident master and a staff of tutors, as well as a dining hall and library, and maintains an active schedule of athletic, social, and cultural events.