Mary Elizabeth Garrett was the daughter of John Work Garrett, the Baltimore and Ohio Railroad president who had been one of Johns Hopkins's closest associates. When she inherited a significant share of the railroad fortune, she organized the campaign to fund the medical school. The terms she negotiated were ironclad: $500,000 raised on the condition that the school admit women on equal terms; that the entering students hold college degrees and demonstrate reading proficiency in French and German; and that women's tuition be the same as men's. The terms set the academic standard for the entire institution at the level Garrett wanted. Three women joined the first class of 1893. Florence Sabin entered later, became the school's first female faculty member, and eventually the first woman elected to the National Academy of Sciences. The four women's Women's Fund Memorial Building, now a campus residence hall, still bears their names.

In 1908 the Carnegie Foundation commissioned the educator Abraham Flexner to survey the state of medical education in the United States and Canada. Flexner visited every medical school in North America - 155 of them - and his 1910 report transformed the field. Flexner held up Johns Hopkins as the model. He recommended that most existing medical schools either reform themselves to the Hopkins standard or close. Within fifteen years, half of America's medical schools were gone. The Flexner Report directly created the modern American medical school: a university-affiliated, science-based program that requires a college degree for admission, links teaching to a research hospital, and trains physicians as residents under supervision after graduation. The Hopkins model became the national standard not because it was imposed but because the Flexner Report convinced everyone with money or authority over medical education that the alternative was inferior.

The school's first faculty included four physicians who shaped twentieth-century medicine. William Henry Welch, the pathologist who became the first dean, brought modern German laboratory science to American clinical medicine. William Osler, the Canadian internist whose textbook The Principles and Practice of Medicine (1892) became the standard internal medicine reference for a generation, invented the medical residency and brought students into the wards. William Halsted, the surgeon, pioneered modern aseptic technique, the use of rubber gloves, and the radical surgical procedures that would define oncology for decades; he also struggled with a cocaine addiction that began when he used the drug as an experimental anesthetic on himself. Howard Atwood Kelly established gynecology as an independent surgical specialty and was among the first to use radium against cancer - sometimes with terrible consequences for patients. All four are immortalized in John Singer Sargent's 1905 group portrait The Four Doctors, which hangs in the Welch Medical Library.

Seventeen of the 29 Nobel laureates affiliated with Johns Hopkins University are tied to the medical school. They include Francis Peyton Rous, who won the 1966 Nobel for his demonstration that viruses can cause cancer; Hamilton O. Smith and Daniel Nathans, who shared the 1978 Nobel for the discovery of restriction enzymes that made genetic engineering possible; David Hubel and Torsten Wiesel, who shared the 1981 Nobel for their work on the visual cortex while at Hopkins as fellows; Peter Agre, who won the 2003 Chemistry Nobel for the discovery of aquaporins; Carol Greider, who won the 2009 Nobel for the discovery of telomerase; Richard Axel, who shared the 2004 Nobel for olfactory receptor research; and Gregg Semenza and William Kaelin Jr., who shared the 2019 Nobel for their work on how cells sense oxygen. Bernard Lown, an MD 1945 graduate, was one of the founders of International Physicians for the Prevention of Nuclear War, which won the 1985 Nobel Peace Prize. The school's research output has been described, accurately, as a national resource.

In July 2024, Michael Bloomberg - the billionaire former mayor of New York City and a 1964 Hopkins undergraduate - announced a $1 billion gift to the medical school. The gift made tuition free for all medical students whose families earn under $300,000 a year, beginning in fall 2024. Bloomberg had previously given more than $4 billion to the university across his lifetime; the medical school tuition gift was structured to address a specific problem that had been corroding American medical education for decades, the immense debt that drives new physicians into the most lucrative specialties rather than the primary care fields where the country needs them most. Whether free tuition will actually shift the specialty distribution remains to be seen. What is clear is that Hopkins now joins NYU and a small handful of other peer institutions in offering tuition-free medical education to most students - a return, in some sense, to what Garrett's $500,000 made possible in 1893: medicine as a public good accessible to the people best qualified to study it, not just those who can afford it.