Highland Hospital opened in 1927 as the first comprehensive, acute care hospital in Oakland. At its opening, it was considered one of the most beautiful hospitals in the West. With its Spanish Baroque architectural style, there was the promise of "progressive medical care in comfortable surroundings" for the citizens of Alameda County.  In 1969, a new hospital building was constructed on the existing site to accomodate growth and to meet the need for more modern facilities.

Currently, the Highland Hospital campus is undergoing a nearly $700 million renovation. Two of the three phases have been completed, including a new ambulatory building (Highland Care Pavilion) and the new Highland Hospital Acute Care Tower, which opened on April 4, 2016.  

The spirit of the original mission, 'to improve the health of all county residents regardless of their ability to pay', still holds true today. As a safety net institution, a level 1 trauma center, and the oldest teaching hospital for Alameda County, Highland Hospital has played a central role in East Bay medicine for almost 90 years.