The settlement that would become modern Pitcairn began to grow on the banks of Turtle Creek in 1841 when farmer John McGinnis began sell land to fellow settlers.
In 1850, the Pennsylvania Railroad purchased a corridor from McGinnis. In 1874, Robert Pitcairn of the Pennsylvania Railroad purchased a further 215 acres in the area to serve as a new hub for the Pittsburgh railyard, the original location of which was deemed too small to support the growing level of rail traffic in the region.
During the late 1800s, the growing settlement was called "Wallurba" by residents. In 1894, the settlement separated from current-day Monroeville (formerly known as Patton Township) and was incorporated as the borough of Pitcairn.
The Pitcairn Rail Yard operated by the Pennsylvania Railroad facilitated the growth of Pitcairn into a robust industrial community during the first half of the 20th century. In 1950, the Pennsylvania Railroad decided to expand the Conway Terminal north of Pittsburgh. This led to a slow decline of the importance of the Pitcairn Rail Yard in the second half of the 20th century, and a subsequent population decline in the borough.
In 1996, the Pitcairn Rail Yard was re-opened as an intermodal facility, operated since 2012 by Norfolk Southern.
Early in the 20th century, Pitcairn was the site of large railroad yards and shops that employed nearly ten thousand men. The population increased from 2,601 in 1900 to 6,310 in 1940, but has since declined. The population was 3,101 at the 2020 census.