The current alignment of PA 652 was classified as a state highway as early as 1920, nine years after the Sproul Road Bill was passed by the Pennsylvania State Legislature. The Sproul Road Bill also assigned the first state highways in Pennsylvania. There was no designation given to the highway.
From 1926 to 1972, the modern routing of PA 652 was part of US 106. The road also carried a portion of PA 19 from 1927 to 1930. On March 14, 1972, US 106 was decommissioned and replaced with the PA 652 designation between Indian Orchard and the Delaware River.