The former U.S. Marine Hospital on Wyman Park Drive near the Johns Hopkins University Homewood campus was built in 1934—but the Marine Hospital Service itself dated back over a century earlier.

In 1798, President John Adams signed "An Act for the Relief of Sick and Disabled Seamen" that supported the creation of Marine Hospitals in major American ports from Boston to Baltimore. Following the Civil War, a scandal broke out over the mismanagement of the Marine Hospital Fund (supported by a tax on the wages of all U.S. sailors). In 1870, the U.S. Congress responded to the controversy by converting the loose network of hospitals into a more centrally-managed bureau within the Department of Treasury.

Early on the Baltimore Marine Hospital was located in Curtis Bay on the same site later developed at the Bethlehem Fairfield Shipyard. The Maryland Hospital of U.S. Marine Hospital Service also maintained dedicated wards at St. Joseph’s Hospital at Caroline and Hoffman Streets before the construction of a new hospital complex on Remington Avenue around 1885. A 1901 directory of Baltimore charities invited sailors in need of medical care to apply for admission at the surgeon’s office located at the Baltimore Custom House, explaining:

Only those who have served as sailors on an American registered vessel for at least 60 days prior to application are strictly eligible, but any bona fide sailor taken sick or injured in the line of duty will receive attention.

In 1934, the old building was replaced by a modern 290-bed facility making Baltimore's hospital the second largest marine hospital in the country. In the 1950s, the hospital began serving a more general population, including both people enlisted in the military and local residents, as the United States Public Health Services Hospital.

In October 1981, the federal government closed all of the U.S. Public Health Service hospitals across the country. Baltimore's old Marine Hospital was taken over by a group known as the Wyman Park Health System and continued to treat many of the patients who had been going there for decades. In 1987, the group merged with Johns Hopkins University. One result of the merger was the creation of a new primary care organization, the Johns Hopkins Community Physicians, that has continued to provide outpatient medical services from the lower levels of the building today.

In 2008, the university considered plans for demolishing and replacing the building. Fortunately, in January 2019, the university announced plans to preserve and renovate the building for continued use by students and faculty.