PA 46 was first signed in 1927, extending from U.S. Route 6 in Smethport north to US 219 in Bradford. The route was extended southward to Emporium in 1928 when the eastern segment of Pennsylvania Route 47, which ran along present-day PA 46 from PA 120 in Emporium to US 6 in Smethport, was decommissioned after only one year of service.