In November 1813, the college agreed to incorporate its medical school with The College of Physicians and Surgeons, a new school created by the Regents of New York, forming Columbia University College of Physicians and Surgeons. The college’s enrollment, structure, and academics stagnated for the majority of the 19th century, with many of the college presidents doing little to change the way that the college functioned. In 1857, the college moved from the King’s College campus at Park Place to a primarily Gothic Revival campus on 49th Street and Madison Avenue, where it remained for the next forty years. During the last half of the 19th century, under the leadership of President F.A.P. Barnard, the president that Barnard College is named after, the institution rapidly assumed the shape of a modern university. Barnard College was created in 1889 as a response to the university’s refusal to accept women. By this time, the college’s investments in New York real estate became a primary source of steady income for the school, mainly owing to the city’s expanding population. University president Seth Low moved the campus from 49th Street to its present location, a more spacious campus in the developing neighborhood of Morningside Heights. Under the leadership of Low’s successor, Nicholas Murray Butler, who served for over four decades, Columbia rapidly became the nation’s major institution for research, setting the “multiversity” model that later universities would adopt. Prior to becoming the president of Columbia University, Butler founded Teachers College, as a school to prepare home economists and manual art teachers for the children of the poor, with philanthropist Grace Hoadley Dodge. Teachers College is currently affiliated as the university’s Graduate School of Education.

Research into the atom by faculty members John R. Dunning, I. I. Rabi, Enrico Fermi and Polykarp Kusch placed Columbia’s physics department in the international spotlight in the 1940s after the first nuclear pile was built to start what became the Manhattan Project. In 1928, Seth Low Junior College was established by Columbia University in order to mitigate the number of Jewish applicants to Columbia College. The college was closed in 1938 due to the adverse effects of the Great Depression and its students were subsequently taught at Morningside Heights, although they did not belong to any college but to the university at large.

There was an evening school called University Extension, which taught night classes, for a fee, to anyone willing to attend. In 1947, the program was reorganized as an undergraduate college and designated the School of General Studies in response to the return of GIs after World War II.[48] In 1995, the School of General Studies was again reorganized as a full-fledged liberal arts college for non-traditional students (those who have had an academic break of one year or more, or are pursuing dual-degrees) and was fully integrated into Columbia’s traditional undergraduate curriculum. Within the same year, the Division of Special Programs—later the School of Continuing Education, and now the School of Professional Studies—was established to reprise the former role of University Extension. While the School of Professional Studies only offered non-degree programs for lifelong learners and high school students in its earliest stages, it now offers degree programs in a diverse range of professional and inter-disciplinary fields.