The current Milwaukee Hospital campus was constructed between 1912 and 1985 atop a hill on Milwaukee's near west side. The campus of buildings is noted for its history of surgical and medical research and education. Early in the hospital's history, Dr. Nicholas Senn gained international acclaim for his antiseptic procedures from 1879 to 1891. In 1912, it was the site of the first use of x-ray technology in Wisconsin and had the city's first intensive care unit. The Milwaukee Hospital campus, the city's second oldest general hospital, opened in 1863 in an old farm house on the ten-acre block. Established by Reverend William Passavant, the Director of the Protestant order of Deaconesses, the hospital first served the city's German community and its primary mission was social welfare.

Beginning in 1902 Reverend Herman Fritschel, the new Director and Rector of Milwaukee Hospital, greatly expanded the hospital and incorporated modern medicinal practices in its administration. Fritschel developed the Milwaukee Hospital School for the Training of Nurses in 1903; installed the state's premier x-ray lab; added several wings, the Maternity Pavilion, and Deaconess Home; and established the first outpatient clinic and first local critical care unit. In the Central Wing, the extraordinary two-story lobby was Fritschel's idea to make the hospital experience more comfortable, recalling the setting of a large hotel.

Fritschel was a pioneer in hospital administration. He helped establish the Milwaukee Hospital Council, served as the president of the Wisconsin Hospital Association, helped found and head the Protestant Hospital Association of America, and collaborated in establishing the American College of Hospital Administrators (now the American College of Healthcare Executives). Fritschel was among the architects of the Blue Cross of Wisconsin hospital insurance plan.

The campus functioned as a hospital until 1995, when the then Sinai Samaritan closed the facility to consolidate its services at its campus near 12th Street. In 2005, the Madison-based Gorman and Company renovated the oldest of the hospital buildings to create an apartment community.