From approximately 1830 to 1903, the section between
Lewisburg and
Mifflinburg was owned and operated by the
Lewisburg and Mifflinburg Turnpike Company. The section west of Mifflinburg (formerly Youngmanstown) was built by the
Bellefonte, Aaronsburg and Youngmanstown Turnpike Company, chartered in 1825. 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. In 1928, the route was under construction from Indianland to Beersville and completed the following year on the Ashland to Easton section. In 1930, the route was paved from
Lehigh Gap to Indianland on the eastern section. In 1934, the eastern terminus was moved from Walnut Street to 13th Street in Easton. In 1932, a western section of PA 45 was opened from
Belsano to
US 22 near
Sankertown and
Cresson. The route replaced
US 422 from Belsano to
Ebensburg and US 22 from Ebensburg to Cresson when those designations were placed on a straighter route. In 1936, the eastern terminus of the middle section was moved from Montandon to
Mausdale. In 1946, the eastern terminus of the western section was truncated from Cresson to Ebensburg. Until 1952, the middle section entered
Mooresburg on a different route. In 1951, construction began on a bypass which opened in 1952. In 1955, the eastern terminus in the eastern section was moved from 13th Street to Third Street in Easton. Until 1961, there was a break between Mausdale and Ashland, that was connected when
PA 54 was truncated to Mausdale. This resulted in PA 45 being a continuous route between Altoona and Easton. This change was undertaken as part of a plan to simplify route numbers across the state. Also in 1961, the western section of PA 45 was decommissioned; the piece of PA 45 between Belsano and
Nanty Glo became part of an extension of
PA 933 and is currently part of
PA 271. In 1962, the route was changed from going into
State College via US 322 and then PA 26, to go straight from PA 26 to
Boalsburg. On May 9, 1966, the eastern terminus of PA 45 was cut back from Easton to its current location at PA 642 in Mooresburg. The former alignment east of Mooresburg became PA 642 between Mooresburg and Mausdale, an extended PA 54 between Mausdale and
Nesquehoning, solely
US 209 between Nesquehoning and
Weissport, and newly-designated
PA 248 between Weissport and Easton. This change was made to remove several concurrencies, while the extension of PA 54 to replace PA 45 between Mausdale and Nesquehoning was made to provide a direct connection with I-80. ==Major intersections==