Founded on lands given to missionaries Hiram and Sybil Bingham by Kaahumanu in 1829, Punahou School's grounds encompass approximately seventy-six acres. The Binghams departed Hawaii in 1840; however, the mission retained possession of these lands, and established a school here in 1842. Although the first students came from missionary families, by 1849 non-missionary children were admitted as well. Initially named Oahu College, the school's name was changed to Punahou School in 1934. One of the school's more famous alumni, U.S. president Barack Obama, graduated in 1979.

In 1917, the school commissioned Bertram Grosvenor Goodhue of New York City to develop a master plan for the campus. Vestiges of that 1921 plan may still be observed in the placement of some buildings on campus, although the entrance and roadways have been reconfigured. Over the course of the school's history, several significant buildings were added. Today the school presents a mix of old and new buildings, some of highly textured intimacy and others of stark institutionality.

The stone wall that runs along the Wilder Avenue side of the school dates from 1830, and is a segment of a larger wall which Kaahumanu had erected from Punchbowl to Moiliili to keep cattle from wandering mauka. The wall is covered with night-blooming cereus,
which was introduced to Hawaii on this wall by Captain Charles Brewer in 1836.