U.S. Route 422 (US 422) is a 271-mile (436 km) long spur route of US 22 split into two segments in the U.S. states of Ohio and Pennsylvania. The western spur of US 422 begins in downtown Cleveland, Ohio, and ends at Ebensburg, Pennsylvania. The eastern spur, located entirely within Pennsylvania, begins in Hershey and ends at King of Prussia, PA, near Philadelphia. U.S. Route 422 Business is the offshoot road into each of 4 towns along the way.

The segmented nature of US 422 violates AASHTO numbering, as two separate roadways traditionally do not carry the same route number. However, the two sections of US 422 are connected by US 22 and US 322, allowing the two halves of US 422 to carry the same designation.

In downtown Cleveland, the western terminus of the western segment of US 422 is at US 6, US 20, US 42, and State Route 3 in Cleveland's Public Square. In Hershey, Pennsylvania, the eastern segment of US 422 begins at an interchange with US 322 and Pennsylvania Route 39 (PA 39). US 422 is named the Benjamin Franklin Highway in Pennsylvania.

Originally, US 422 was routed along existing roads, but much of the route now runs along purpose-built alignments.

The western section of US 422 begins at the center of Cleveland's Public Square in the downtown district. US 422 and State Route 14, which shares its western terminus with that of US 422, form a concurrency as the roadway heads south from the square. Less than a mile from the Public Square, US 422 and SR 14 intersect the Cleveland Innerbelt, the confluence of Interstate 90 (I-90) and the northern termini of I-71 and I-77. US 422 and SR 14 split at the interchange as SR 14 turns south to join State Route 43. State Route 8 begins at the eastern terminus of the US 422/SR 14 overlap, forming a concurrency with US 422 along Woodland Avenue.

US 422 runs easterly along Woodland Avenue and Kinsman Road, through the Kinsman neighborhood. As it crosses Cleveland's city limits just west of Lee Road in Shaker Heights, the street name changes to Chagrin Boulevard, named for the Chagrin River and Chagrin Falls (the eastern terminus of the boulevard) in Cleveland's eastern suburbs. Today, US 422 in Shaker Heights and Beachwood, where it now merges with I-271, is almost a linear edge city, with millions of square feet in office space centered on this corridor. It is one of the busiest streets in Cuyahoga County and Greater Cleveland. It serves as the primary commercial district for the wealthiest pocket of communities in Northeast Ohio.

At Northfield Road, SR 8 turns to the south, leaving US 422 to continue east along Chagrin Boulevard. Two miles east of SR 8 in Beachwood, US 422 intersects State Route 87 and State Route 175, running concurrent with the former for two blocks to I-271 exit 29. Here, US 422 departs SR 87 and Chagrin Boulevard at the southbound ramp to I-271 and joins the expressway southward for 2.5 miles (4.0 km). At Exit 27, US 422 splits from I-271 and proceeds through the eastern suburbs of Cleveland as a limited-access highway, exiting Cuyahoga County and entering Geauga County.

In Auburn Township, US 422 returns to grade-level upon crossing the LaDue Reservoir. The route continues to the southeast, cutting through northeast Portage County and then entering Trumbull County, where US 422 runs through the center of Warren and Girard. The section from downtown Warren to State Route 46 is known as "The Strip" and is lined with shopping centers, fast-food restaurants and other retail establishments. In the 1960s and 1970s, nightclubs along The Strip attracted top-name entertainers. Eastwood Mall is one of two large shopping malls located near US 422, along with the King of Prussia Mall in King of Prussia, Pennsylvania.

Farther southeast, US 422 enters Youngstown, Mahoning County before entering Pennsylvania.

US 422 enters Pennsylvania eight miles (13 km) northwest of New Castle. The route proceeds to the east, passing through the counties of Lawrence, Butler, Armstrong, Indiana, and Cambria County, in the western portion of the state. Major cities along the route include New Castle, Butler, Kittanning, and Indiana, Pennsylvania.

West of Ebensburg, US 422 terminates at an interchange with US 219; a sign directs truck traffic to US 22 to use US 219. The former right-of-way of US 422 continues through Ebensburg to US 22 on the eastern edge of town.

The eastern section of US 422 begins at an interchange with US 322 and PA 39 in Hershey near the Hershey Medical Center and just outside Hummelstown. US 422 proceeds east as a two-or-three-lane highway, traveling through Palmyra, Annville and Cleona. In Lebanon, US 422 departs Cumberland Street to southbound 12th Street then turns left onto Walnut Street as its eastbound alignment. (Cumberland Street is its one-way westbound alignment.) It returns to a two-to-three-lane road east from Lebanon to Myerstown, and Wernersville prior to entering the Berks County city of Reading.

In West Lawn, outside of Reading, US 422 interchanges with the limited-access US 222. US 422 Business, the former routing of US 422 through the city, continues along the right-of-way of US 422 while US 422 merges with the expressway. The US 222/US 422 concurrency travels northward through the immediate western suburbs of Reading before separating at an interchange with PA 12 on the bank of the Schuylkill River. US 222 turns to the west to bypass Reading to the north while US 422 passes to the immediate south of downtown, paralleling the Schuylkill as it heads east.

Southeast of Reading, US 422 meets the northern terminus of I-176 in Cumru Township. Two miles to the east in Lorane, US 422 intersects the eastern terminus of US 422 Business by way of an interchange, and returns to grade-level there.

East of an intersection with PA 662 in Douglassville and 1.5 miles (2.4 km) west of the Berks-Montgomery county line, US 422 separates from the Benjamin Franklin Highway and becomes the limited-access Pottstown Bypass (colloquially known as the "422 Bypass" or simply "The Bypass"). Following the Stowe exit, US 422 crosses the Schuylkill River entering the Chester County census-designated place of South Pottstown and interchanges with PA 100, and later, still near Pottstown, re-crosses that river.

Midway between Pottstown and Limerick, US 422 passes the Pottstown Limerick Airport, one of numerous local airports in eastern Pennsylvania. On the west side of the road, US 422 passes a commercial outlet center, the Philadelphia Premium Outlets, built in 2007.

US 422 passes Royersford, Collegeville (home to Ursinus College and a branch of the pharmaceutical giant Pfizer) and Oaks, and provides access to the sprawling Oaks Corporate Center office park on Egypt Road, then continues to Trooper, and finally arrives at its eastern terminus at an interchange with US 202 in King of Prussia, an area where heavy traffic caused by commuters traveling into Philadelphia during each weekday morning rush hour often causes severe traffic jams.[citation needed]

The terminus of US 422 in King of Prussia is accessible from a number of major roadways in the area, including the Pennsylvania Turnpike, the Schuylkill Expressway, and US 202. The terminus is adjacent to the Valley Forge Turnpike interchange, one of the most notable on the Turnpike as the exit marks the location where I-76, which in Pennsylvania runs concurrent with the Turnpike mainline west of Valley Forge, separates from the Turnpike and turns southeast to Philadelphia as the Schuylkill Expressway, while the Pennsylvania Turnpike continues east to New Jersey as I-276 (and, in the near future, I-95).

The western segment was first signed in 1926.

Most of the highway in Ohio still runs along its original alignment. The section in Parkman Township, Geauga County was twinned during World War II. The four-lane divided highway was extended to Warren by 1950. In 1971, an expressway bypass around downtown Youngstown opened.

The divided highway portion of US 422 connecting downtown Solon to I-271 and I-480 was originally signed as US 422 Alternate. In 1991, the freeway was extended eastward through Bainbridge Township across the LaDue Reservoir to State Route 44 in Auburn Center, and US 422 was rerouted along I-271 and the former US 422 alternate. The new freeway made US 422 a popular route for truckers and commuters and made the remaining two-lane portion in Geauga County particularly dangerous. The state has added traffic lights, rumble strips and extra width to the road to try to alleviate some of the danger.

Prior to the realignment, US 422 originally ran along Chagrin Boulevard (formerly Kinsman Road) through Woodmere, Pepper Pike, Moreland Hills, Chagrin Falls and Bainbridge Township.

The expressway bypass of Butler was built in the early 1960s. Previously, the road ran through downtown Butler. The section that runs through Moraine State Park near Butler was upgraded to expressway standards in 1969. In the 1970s, bypasses were built around the cities of New Castle, Kittanning and Indiana. Sections of the Indiana bypass remained incomplete until 1995 and the Kittanning bypasses were completed in 2000. Part of the bypass in New Castle is now part of the Interstate Highway System, as a recent extension of I-376 runs concurrent with US 422 for three miles (5 km).

In the 1960s, US 422 in the Reading area was rerouted from surface streets through downtown Reading onto bypasses built south of the city. The former routing of US 422 through the city became US 422 Business.

Before it became highways, US 422 ran on surface roads through Pottstown and Sanatoga (High Street),Limerick and Collegeville (Ridge Pike, occasionally referred to locally as "Old 422"), Plymouth Meeting, and the Germantown section of Philadelphia (via Germantown Pike and Germantown Avenue), terminating in different places in Philadelphia over time. In 1965, the highway route of US 422 was extended 8.4 miles (13.5 km) east with the "Pottstown Bypass", following the Schuylkill River and terminating at Township Line Road in Sanatoga. At the same time, a segment of highway was built from King of Prussia to Trooper, terminating at the Betzwood Bridge. It took roughly another twenty years for the remaining segments between Sanatoga and Trooper to be completed, finally connecting the highway route to King of Prussia. (Eastbound on US 422, the median strip widens just after the Sanatoga exit, as the road leaves the old Pottstown bypass.)

In the first decade of the 2000s, this segment of US 422 saw traffic volume increase by 50%. Volume reached 45,000 vehicles per day at Pottstown, and 110,000 vehicles per day at the bridge crossing the Schuylkill.

At the federal level, the Schuylkill Valley Metro was proposed to connect Philadelphia to Reading. This rail service would parallel US 422 from King of Prussia into Berks County. It failed when the bloated price tag of $1.3 billion did not receive federal funding in 2006.

Construction of a third westbound lane between PA 23 and PA 363 began in February 2008 and was completed roughly a year later. The project restructured the Route 23 interchange and squeezed three westbound lanes onto the existing Schuylkill River crossing, using 11-foot (3.4 m) lanes and a narrower median guard.

Local planning commissions then created a "US 422 Corridor Master Plan". This plan addressed the future trends of traffic on US 422 through a set of sustainability programs, a proposed extension to SEPTA's Manayunk/Norristown Line regional rail service to Wyomissing (a restoration of rail service between Norristown/Reading/Pottsville that SEPTA abruptly terminated in July 1981), and additional road construction. The plan's rail and construction projects would be funded by tolling the highway. Tolls would be charged on a per-mile basis; driving the entire segment between Pottstown and King of Prussia would cost $2. All tolls would be electronically collected via the E-ZPass electronic toll collection system. The plan was debated in local municipalities during 2010, with many adopting the sustainability portions of the plan while objecting to the charging of tolls. On October 5, 2011, under increasing pressure and opposition, DVRPC cancelled the tolling proposal and stated that the highway would be expanded under regular PennDOT programming instead.

In the early 2000s, the US 422, US 202, and I-76 interchange in King of Prussia underwent a massive five-year reconstruction project that involved the construction of new ramps and the widening of all intersecting roadways. Several small businesses in the King of Prussia area were demolished as part of this project: the nearby King of Prussia Mall shopping complex was also affected.

In New Castle, U.S. Route 422 Business is a 7-mile (11 km) route following the original alignment of its parent. At its western edge, the route leaves the freeway and travels as a four-laner along the Beaver River. Amongst a combination of residences and light industry, the route confusingly meets US 224. Winding its way through the city center, the route changes directions several times as it functions as portions of State Street, Jefferson Avenue, Washington Street, and, in a more tree-lined residential area, Butler Street. Closer to its eastern edge, it passes commercial development, and 422 Business joins with US 422 as its freeway segment ends.

In Kittanning, U.S. Route 422 Business is a 5-mile (8.0 km) route following the original alignment of its parent. It begins in the west with a cosignment with PA 286, before arching around commercial development in West Kittanning and crossing the Kittanning Citizens Bridge. After serving as the major Water Street, the route winds out of Kittanning toward the edge of the bypass.

In Indiana, Pennsylvania, U.S. Route 422 Business is a 7-mile (11 km) loop around Indiana, Pennsylvania. Despite functioning as a business route for a freeway bypass, the road does not completely follow its parent's original path, nor does it enter the city center. It instead encompasses a much more rural path, starting in the west on Pike Avenue near the outskirts of Indiana, then corresponding with Warren Road and Indian Springs Road, before reaching some development on Wayne Avenue, as it meets back up with the freeway.

In Reading, U.S. Route 422 Business is a 7-mile-long (11 km) auxiliary route of US 422 located in the Reading, Pennsylvania area. The route is one of four auxiliary routes of US 422 in Pennsylvania. Its western terminus is at an interchange with US 222 and US 422 in Wyomissing. Its eastern terminus is at an interchange with US 422 in Reiffton.