While the majority of African Americans lived in the South, they were excluded from many public and private racially segregated institutions of higher education, particularly after the end of Reconstruction.

In the early 21st century, it has become the largest private historically black institution in the United States solely dedicated to educating health care professionals and scientists.

Meharry is the second-largest educator of African-American medical doctors and dentists in the United States.

[10] Because of segregation, most hospitals would not admit African Americans, and many white physicians often chose not to serve freedmen.

[11] The college was named for Samuel Meharry, a young Irish American immigrant who first worked as a salt trader on the Kentucky-Tennessee frontier.

[5] After achieving some success, he and four of his brothers later made a major donation to help establish the college.

[13] In 1875, Meharry, together with four of his brothers, donated a total of $15,000 to assist with establishing a medical department at (CTC), a historically black college in Nashville, Tennessee.

[14] With the contribution of the Freedman's Aid Society of the Methodist Episcopal Church North, George W. Hubbard and Braden,[15] they opened the Medical College at CTC in 1876 with a starting class of nine students.

[12] The Medical College remained in its original buildings, and Walden University moved to another campus in Nashville in 1922.

Abraham Flexner of the General Education Board (a Rockefeller program) provided advice and funding to rebuild its status.

As a result in 1923, Meharry was restored to a "grade-A institution" by the American Medical Association (AMA).

[12][27] Since its founding, Meharry Medical College has added several graduate programs in the areas of science, medicine, and public health.

[19] By the late 1960s and early 1970s, 83 percent of all African American physicians had been trained at Meharry Medical College and Howard University School of Medicine.

[31] In 1972, Meharry started receiving federal distress grants which were given to medical schools with deficits in operating costs and problems with accreditation.

[37] In 2005, Meharry was censured by the American Association of University Professors for not observing generally recognized principles of academic freedom and tenure.

[40] Meharry students had previously received clinical training at numerous sites, primarily Nashville General Hospital, which had moved on-campus in the 1990s.

[41] Withdrawal of the alliance with Meharry is thought to threaten the provision of inpatient care at Nashville General Hospital.

[43] In April 2019, then-dean and senior vice president of health affairs Dr. Veronica Mallett secured a partnership with Detroit Medical Center to increase the number of Meharry students able to complete their studies at that hospital.

[45] In September 2020, philanthropist Michael Bloomberg donated $34 million to help lower student debt at the institution.

[51] [52] George W. Hubbard served as Meharry Medical College's first president from its founding in 1876 until his retirement in 1921.

He added a new wing to Hubbard Hospital, eliminated the nursing and the dental technology programs, and purchased land adjacent to the campus for expansion.