Twenty-six local people, mostly former members of the Old South Meeting House, wanted to create a church with orthodox Trinitarian theology.

The church's cornerstone was laid on May 1, 1809, and construction was completed by the end of the year, under the guidance of Peter Banner (architect), Benajah Young (chief mason) and Solomon Willard (woodcarver).

[6] Park Street Church has a strong tradition of missions, evangelical doctrine, and application of Scripture to social issues, as well as a notable list of firsts.

Edward Dorr Griffin (1770–1837) served as the first pastor of the Park Street Church and preached a famous series of Sunday evening sermons attacking the New Divinity.

On July 4, 1829, William Lloyd Garrison delivered his Address to the Colonization Society at Park Street, making his first major public statement against slavery.

[9] Park Street also played a role in founding the first "Homeland" or American Mission to the Sandwich Islands (now Hawaii), where that church still stands; the Handel and Haydn Society started there.

Harold J. Ockenga, notable theologian and co-architect of the (Neo-)Evangelical movement was the senior pastor from 1936 to 1969, and during this time co-founded Gordon-Conwell Theological Seminary with Billy Graham, co-founded Fuller Theological Seminary, the National Association of Evangelicals, War Relief (which later became World Relief), and the Christian publication Christianity Today.

Designed in a modernist architectural style by Stahl/Bennett Associates with a concrete structure, window-walls and purplish brick facing, the building is described by the Boston Preservation Alliance as follows: "The Church Ministries Building Addition to Park Street Church breaks dramatically with its surroundings in style, while relating coherently to it in materials.

For example, Park Street Church helped launch a private high school in Hyde Park, Boston Trinity Academy, in 2002, to help address the educational needs of inner-city Boston (more than 70% of its students are on scholarship and more than 50% are minorities); it hosts many English as a Second Language classes during the week;[13] it has and supports ministries for the homeless, such as Boston Rescue Mission, and Park Street's HOME ministry on Thursday evenings and Saturday mornings;[14] it partners with crisis pregnancy centers Daybreak Pregnancy Resource Center and A Woman's Concern; it provides English classes for international students and immigrants.