A median was installed in 1966 in Newtown Square, in Goshen Road, and in Wyola when the interchange with Newtown Road was completed.  In 1969, the northern terminus was moved from US 202 at King of Prussia to its current location via Waterloo Road from south of Leopard.

In 1970, the route was changed to its current location between Wyola and PA 23.  A median was installed at US 1 in 1978.

In 1941, the section from the Northumberland County line to Hagenbuch Road was paved.  In 1946, the section from Hagenbuch Road to Diehl Road was paved.

Until 1952, the eastern terminus was PA 44 in Jerseytown, and then was extended to Red Rock.  In 1966, it was moved to its current location.

In 1946, the designation was moved to its current alignment between DuBois and Shaffer.  Previous to that it started at US 219 in DuBois and traveled Park Avenue, Maple Avenue, and Shaffer Road.

In 1975, the highway was widened and a small median installed between PA 948 and Saint Marys.

In 1946, the northern terminus was moved from US 62 at Wilson Avenue via East Fourth Street and Allegheny Avenue in Oil City to its current location.

In 1955, the southern terminus was moved from Freedom to Rockland.  In 1958, the southern terminus was moved to its current location.

Until 1976, the northern terminus was at US 1 in Chester Heights.  It continued on past the current terminus via Foulk Road and Valleybrook Road.

A median was installed in 1964 from the Montgomery County line to Warminster.  Work began on a new alignment east of Hartsville in 1968 and opens in 1969. 

Work to widen and divide the highway between Hartsville and Buckingham began in 1970 and finished in 1972.  It wouldn't be until 1990 that the remaining section from Warminster to Hartsville would see a median. 

In 1950, the Western terminus was moved from Whiteley Maple to PA 21.  A ferry across the Monongahela River between Greensboro and New Geneva to continue the designation between Greene and Fayette Counties.

In 1931, the route was under construction from Auburn Center to Carter Road and opened a year later.  In 1932, the route was paved from Carter Road to Lawton and Stanley Lake Road to Choconut.

In 1931, the route between Parker and Emlenton was under construction and was completed the following year.  In 1932, the section between Browns Crossroads and Karns City was paved.

In 1982, with the completion of the Kittanning Bypass, the southern terminus was moved to its current location from downtown West Kittanning.

The first change to the route took place in 1961 when the southern terminus was moved from US 30 in Ligonier to its current location.  Six years later, the northern terminus was moved from Johnstown to its current location.

In 1965, the northern terminus was moved to Lancaster from Wakefield.  In 1975, the northern terminus was moved from Willow Street to the connector to the Pennsylvania Turnpike.   In 1978, the northern terminus was moved to its current location.

During the later half of September 2009, crews hauled twin 510-ton generators through Lancaster County en route to their new home at Three Mile Island.  The convoy began traversing PA 272 on September 15 and only moved approximately three miles a day until September 18 when it turned onto PA 741 in Willow Street.

In 1930, the route was paved from New Germantown to Blain.  In 1931, the route from PA 75 to New Germantown was under construction and completed the following year.  In 1936, the eastern terminus was moved from New Bloomfield to its current location.

In 1949, the section from the Mount Joy interchange to PA 72 opened.  In 1951, construction began on the section from PA 72 to US 30, and opened in 1952.

From 1961 to 1969, the route was revived and signed on Eisenhower Boulevard from PA 230 in Highspire to I-83 in Paxtang to replace the decommissioned Bypass US 230 designation.

In 1967, construction began from east of Elizabethtown to the Mount Joy interchange.  In 1969, construction extended from Eisenhower Boulevard to east of Elizabethtown.

In 1971, the designation was revived for the Harrisburg-to-Lancaster expressway project.  In 1972, the section from Eisenhower Boulevard to PA 743 opened to traffic and marked the completion of the expressway.

On May 5, 2017, Governor Tom Wolf, Secretary of Transportation Leslie S. Richards, and Pennsylvania Turnpike Commission CEO Mark Compton kicked off a project to rehabilitate the expressway between Eisenhower Boulevard and PA 341.  The $89 million project included total reconstruction of the highway and rehabilitation of 11 bridges (8 mainline and three overhead spans).

Part of the project included reconfiguring the former cloverleaf interchange between PA 283 and Interstate 283.  A new ramp was built following the curve of the I-283 southbound to PA 283 eastbound ramp and a traffic signal was installed at the western end of the bridge over the Interstate for the new connection.  The new ramp, built to eliminate weaving between traffic exiting to PA 283 eastbound and entering from PA 283 westbound in the congested area at the Harrisburg East Interchange of the Pennsylvania Turnpike, opened to traffic on December 12, 2019.  The former PA 283 westbound to Interstate 283 southbound ramp was then demolished.  The project finished in November 2020.

In 1946, the section from New Lebanon to Bodine Corners and from Niles to US 62 was paved.  In 1947, the section between Bodine Corners and Niles was paved.  In 1952, the section from Greiser Road to Conneaut Lake was paved.

In 1971, the route was moved to its current alignment from Hartstown Road to Conneaut Lake.  Prior to that it traveled down Hartstown Road then formed a multiplex with US 322 from Hartstown to Conneaut Lake.  Also, in that year, the section from Hartstown Road to Greiser Road was paved.  In 1972, the route's eastern terminus was moved from US 62 west of Franklin via US 19 and Georgetown Road to its current location.

In 1961 it was signed on its current alignment.  In 1977, the new alignment from Middlebury Center to east of Tioga opened.  The original alignment north of Holliday lies under Hammond Reservoir, named after the town that was eliminated with the reservoir project.  With the opening of the US 15 expressway in 1978, the northern terminus was moved from Tioga the interchange with US 15 just north of the Tioga Reservoir.

When the new section of US 15 was completed to the New York state line in 2008, the northern terminus moved again to its current location.

In 2006, the designation was revived to provide a loop for traffic from I-90 to I-79 and use the 12th Street corridor as an east-west alternative to the congested Bayfront Parkway.

The designation was moved from Penrose Avenue, Moyamensing Avenue, and Broad Street to Essington Avenue and Passyunk Avenue in 1952.  The eastern terminus was moved from Spring Garden Street to City Hall in 1954.  A median was installed in 1958 from Eddystone to Philadelphia.

The eastern terminus moved to I-76 in 1987.  Also that year, a median was installed on 26th Street.

In 2003, the eastern terminus was moved onto 26th Street to end at I-76, instead of continuing to I-76 on Moyamensing Avenue.

On October 2, 2006, the designation was moved from Industrial Highway and Penrose Avenue in front of the Philadelphia International Airport and onto Bartram Avenue.  The reason for the shift was due to expansion of the airport.

Rehabilitation of the George C. Platt Bridge in southwest Philadelphia began in May 2011 and concluded in 2014.  The $42.8 million project consists of repairing the structural steel, replacing expansion joins, repairing concrete piers, rehabilitating and resurfacing the bridge and approaches, replacing guide rail and damaged pedestrian railings, and painting the structural steel.

A fire broke out at the Philadelphia Energy Solutions refining complex around 3:20 AM on the morning of June 21, 2019.  The Platt Bridge was closed to all but emergency vehicles while the blaze raged, but was reopened to all traffic just before 6 AM.

SR 0295 is currently assigned to Interstate 295.