The first Post Office in Pittsburgh was founded in 1787 and located on the corner of Market and First Streets, in the home of John Scull. Weekly mail service between Pittsburgh and Philadelphia was established in 1795. The mail traveled by stagecoach and was handled out of the old Market House.

The first official Post Office in the city of Pittsburgh was built in 1892 at the corner of Fourth Avenue and Smithfield Street. In 1934, the current Post Office on Grant Street was dedicated.

The old Allegheny Post Office, built in 1897 on the North Side, served the northern residents until the late 1960s. The aging building was purchased by the Pittsburgh Historic and Landmarks Foundation. The Foundation created a city history museum in the building, in the 1970s. On June 12, 1983, the newly-established Pittsburgh Children's Museum opened in the basement of the Old Post Office Museum. By 1987, the Children's Museum occupied all three floors of the building.