Members of the New Guinea community began building the Meeting House in 1823, but the building was not yet finished on January 4, 1825, when it was consecrated as a place of worship.

In March of 1825, the Trustees of the School Fund for the Coloured People received a deed for the land on which the Meeting House stood. The trustees paid the token sum of $10.50 to prominent New Guinea businessman Jeffrey Summons, agreeing to a proviso that “a school to be kept in it [the African Meeting House] forever.” By mid-April 1825 classes were being held there.
In 1827, with the building already in use for two years, Absalom Boston in his capacity as secretary of the trustees of the African School, wrote a fund-raising appeal for means to finish the interior and install seating.
From the first, the African Meeting House was a multipurpose center. It housed both the African Baptist Church (later renamed the Pleasant Street Baptist Church) and the African School, and it was used as a community center for neighborhood gatherings.
Following the success of a years-long effort in the 1840s to racially integrate the Nantucket Public Schools, the African School went out of existence, but the building continued as a church and community center.
The last religious service in the African Meeting House took place in 1910, and the building was closed as a place of worship in 1912. After many years of use for other purposes, it was restored and reopened to the public in 1999.