When the W.I. Cook Memorial Hospital opened in 1929, it was a medical facility for the general population that offered services for all, without regard for the patient's ability to pay. In 1952, the facility changed focus to conentrate only on children's medical services. It was in that year, the name was changed to W.I. Cook Children's Hospital.
The building was designed by Wiley G. Clarkson and was built by Harry B. Friedman. They also teamed up to work on the Masonic Temple across the street, a few years later. The buidling is eclectic in design and features Romanesque and Renaissance elements. The building is constructed out of Indiana Limestone, Italian travertine, and green terracotta roof tiles. When the building opened in 1929, it featured a central three story tower in the shape of a "H" with a projecting one story wing orienting toward a courtyard between the buildings. From the street view, this wing had six sides. In 1958, two floors were added to the one story wing that matched the materials and architecture of the lower floor.
In 1985, the building was purchased by HealthSouth in anticipation of the hospital's move to their new location. In 1990, a three story addition to the north side of the building was constructed. The architects for this addition were Gresham, Smith & Partners. The Frymire Co. was the contractor for this project. The courtyard within the front wing was roofed over at this time and a large skylight was placed over the new atrium.