 When Pennsylvania's "traffic routes" were established in 1925, PA 45 was originally signed from Herndon to Easton.The 1928 revision expanded this route westward; PA 45 was signed on two different sections, the connection between them being signed as part of US 120 (later US 122, now PA 405, PA 147, and PA 61).The "middle" section was signed from Water Street to Montandon, between Milton and Northumberland, and the east section from Ashland to Easton.