In 1932, the route between Ohio and PA 551 and New Galilee and Darlington was paved.  In 1936, the eastern terminus was moved from Darlington to the current location.  Also that year, the route from Koppel to Ellwood City opened.

In 1930, the section from Braeburn Road to Freeport was paved.  In 1932, the section from PA 56 to Braeburn Road was paved.

In 1941, the route was moved from Neupert Road, Water Street, and Saxonburg Road between Hannahstown and Butler to its current alignment.  In 1946, the southern terminus was moved to its current location from PA 56 in Weinels Crossroads.

In 1972, the northern terminus was moved from Main Street in Butler to its current location.

In 1954, it was moved back to Greenville.  In 1964, the eastern terminus was moved from Greenville to its current location.

Signed in 1946.

In 1950, the southern terminus was moved from PA 23/PA 83 in Valley Forge Park to Port Kennedy.

In 1961, the southern terminus was moved from Port Kennedy to US 202.  In 1967, the southern terminus was moved from US 30 in Devon to US 202 in King of Prussia via the US 422 expressway.

In 1985, the southern terminus was moved from US 202 in King of Prussia to the current location.

Signed on the current PA 144 alignment from State Camp to Renovo from 1928 to 1930 as well as from Orviston to Beech Creek.  In 1930 the designation was moved to the alignment above and paved in 1932.

In 1961, the western terminus was moved from Seventh Street in New Kensington to Tarentum via Stevenson Boulevard.  In 1962, the tolls were removed from the Tarentum Bridge over the Allegheny.

In 1970, construction began on the PA 366/PA 380 cloverleaf, which finished in 1972.

In 1934, the section between Parker and Perryville Road was under construction.  In 1935, that section opened and the designation moved off Perryville Road.

In 1967, the eastern terminus was moved from PA 68 in Silgo to its current location.

In 1946, the eastern terminus moved from PA 570 in Preston Park to then PA 90, now PA 191.

In 1950, the sections from Niagara to Turner Road and Rileyville to Holgate Road was paved.  In 1954, the western terminus was moved from US 11 in New Milford via Great Bend Turnpike and the current PA 848 alignment.

The eastern terminus moved from Christiana to Coatesville in 1946.

Construction on the bridge over the Susquehanna River began in 1967 and opened in 1968.  With that, the western terminus was moved from McCalls Ferry to its current location.

Construction from West Broad Street to US 22 began in 1966 and finished in 1968.  At that time, the segment received the Interstate 378 designation.

Signed in 1971 after I-378 was decommissioned.  In 1974, the designation replaced PA 191 from Center Valley to Third Street in Bethlehem.  

In 1930, the route was paved from Perrysville to PA 80.

In 1964, the western terminus was moved from Penn Avenue in Wilkinsburg to Pittsburgh at the Fort Pitt Bridge.  In 1969, work started on a new alignment from Crestview Drive to PA 66 that opened in 1970.

In 1970, construction began on the PA 380/PA 366 cloverleaf, which finished in 1972.  Originally ended at the interchange of I-279 and I-376 until 1985.  That year the route was removed from Liberty Avenue and Seventh Street in downtown Pittsburgh and the western terminus moved to its current location.

Signed in 1961 on its current alignment.

In 1936, the route was moved from the current PA 65 alignment between New Brighton and New Castle to its current location.

In 1940, the section from Frew Mill Road to PA 168 was improved.  In 1941, the section from US 442 to PA 108 was paved.  In 1946, the section from PA 108 to PA 168 was paved. 

In 1940, the section from the Monroe County line to Roemersville was paved.  In 1948, the section in Roemersville was paved.  In 1949, the section from Roemersville to north of Promised Land State Park was paved.

Signed in the current location in 1961.