Several special routes of U.S. Route 25 (US 25) exist. In order from south to north, they are as follows.

Statesboro bypass route

U.S. Highway 25 Bypass (US 25 Byp.), in complete concurrency with State Route 67 Byp. (SR 67 Byp.), is the western half of the divided four-lane bypass, west around Statesboro, Georgia, also known as "Veterans Memorial Parkway". The eastern half is US 301 Byp., which is in concurrency with SR 73 Byp. The entire length of US 25 Byp. is part of the National Highway System, a system of routes determined to be the most important for the nation's economy, mobility, and defense.^[2]

Waynesboro bypass route

U.S. Highway 25 Bypass (US 25 Byp.), in complete concurrency with SR 121 Byp., is a divided four-lane bypass, east around Waynesboro, Georgia. Only the southernmost portion of US 25 Byp. is part of the National Highway System, a system of routes determined to be the most important for the nation's economy, mobility, and defense.^[2]

Augusta–North Augusta business loop

U.S. Route 25 Business (US 25 Bus.) is a 4.4-mile-long (7.1 km) business route of US 25 that connects Augusta, Georgia, with North Augusta, South Carolina. Its Georgia portion is part of Broad Street and 13th Street. Its entire South Carolina portion is part of Georgia Avenue. In Georgia, it is concurrent with SR 28 for one block and SR 4 for about 0.3 miles (0.48 km). In South Carolina, it is concurrent with South Carolina Highway 125 Truck (SC 125 Truck).

US 25 Bus. begins at an interchange with US 1/US 25/US 78/US 278/SR 10/SR 121 (Gordon Highway) on the line between the Olde Town portion of the city of Augusta and downtown. Northbound traffic on US 25 Bus./SR 28 has to make a U-turn to access Gordon Highway. Here, the business route is concurrent with SR 28. The two highways travel to the west-northwest. The next intersection is with 5th Street, which leads to the Riverwalk Marina. At this intersection, SR 28 departs to the left, heading toward the Government Center and an intercity bus station. On the southeastern corner of this intersection is the former location of the Haunted Pillar. An intersection with 6th Street leads to the Augusta Museum of History, Riverwalk Augusta, and St. Paul's Church. In the middle of this intersection is a crossing of some railroad tracks of Norfolk Southern Railway. An intersection with 7th Street leads to the Woodrow Wilson Boyhood Home and James Brown Arena. Between 7th and 8th streets, the highway passes the Augusta Confederate Monument, the Lamar Building (the tallest building in the city), and the Imperial Theatre. 8th Street leads to the William B. Bell Auditorium. Between 8th Street and James Brown Boulevard, it passes the Augusta Commons Park, a James Brown statue, and the Richmond County Board of Education building. James Brown Boulevard leads to the Augusta-Richmond County Public Library, the Augusta Convention Center, and Riverwalk Augusta. An intersection with 10th Street leads to the Morris Museum of Art and Riverwalk Augusta. An intersection with 12th Street leads to the Museum of Black History and Springfield Village Park. At an intersection with SR 4 (13th Street), which leads to the Sacred Heart Cultural Center, Meadow Garden, and the Medical District, US 25 Bus. turns right, off of Broad Street and onto SR 4 (13th Street). US 25 Bus. and SR 4 travel to the north-northeast on 13th Street. They intersect Jones Street, which carries the eastern terminus of the eastbound lanes of SR 104. The next intersection is with Reynolds Street, with carries the eastern terminus of the westbound lanes of SR 104. US 25 Bus. and SR 4 encounter an entrance to the New Bartram Trail before beginning to travel over the Savannah River on the James U. Jackson Memorial Bridge. About in the center of this bridge, SR 4 and 13th Street end at the South Carolina state line, and US 25 Bus. continues to the north-northeast on Georgia Avenue.

Almost as soon as US 25 Bus. crosses the river, it travels over The River Golf Club. It then curves to the north-northwest. Just south of an intersection with the northern terminus of Center Street, it passes the City of North Augusta Municipal Building. Center Street leads to this building, Brick Pond Park, and the Riverfront. Just north of this intersection, the highway curves back to the north-northeast. Just north of Clifton Avenue, it passes Wade Hampton Veterans Park. The business route then intersects the eastern terminus of West Buena Vista Avenue, which leads to Riverview Park and Lions Field, and the northern terminus of SC 125 (the western terminus of East Buena Vista Avenue), which leads to the public safety complex and community center. At this intersection, SC 125 Truck begins, concurrent with US 25 Bus. An intersection with Spring Grove Avenue leads to the living history park and North Augusta Elementary School. At an intersection with the eastern terminus of Jackson Avenue, the highway curves to the northeast. Just south of Forest Avenue, they pass a memorial for the Hamburg massacre. Just north of this intersection is Lookaway Hall. They then intersect SC 230 (Martintown Road). Here, SC 125 Truck leaves the business route. Just northeast of an intersection with the eastern terminus of Butler Avenue, US 25 Bus. begins to curve back to the north-northeast. On this curve, it passes Davenport Park. Just north of Observatory Avenue, it passes the studio and office facility of WRDW-TV. The highway then passes a U.S. Post Office. North of Five Notch Road, US 25 Bus. curves to the east and reaches its northern terminus, an intersection with US 25/SC 121 (Knox Avenue) and the western terminus of Chalet North Road.

The following portions of US 25 Bus. are part of the National Highway System, a system of routes determined to be the most important for the nation's economy, mobility, and defense:

• The entire length of the SR 28 concurrency^[6]
• From the southern end of the SR 4 concurrency to the northern terminus^[6][7]

Major intersections

State	County	Location	mi[8][5]	km	Destinations	Notes
Georgia	Richmond	Augusta	0.0	0.0	US 1 / US 25 / US 78 / US 278 (SR 10 / SR 121 / Gordon Highway) / SR 28 east (Broad Street east) – Louisville, Waynesboro, Columbia, Beech Island, Augusta Regional Airport	Southern end of SR 28 concurrency; southern terminus; northbound traffic must make a U-turn to access Gordon Highway; interchange
			0.1	0.16	SR 28 west (5th Street) – Government Center, Riverwalk Marina, Intercity bus station	Northern end of SR 28 concurrency
			1.1	1.8	SR 4 south (13th Street south) / Broad Street west – Sacred Heart Cultural Ctr., Meadow Garden House Musm., Medical District	Southern end of SR 4 concurrency
			1.2	1.9	Jones Street (SR 104 east)	Eastern terminus of eastbound lanes of SR 104 on a one-way street
			1.2	1.9	SR 104 west (Reynolds Street) to I-20	Eastern terminus of westbound lanes of SR 104 on a one-way street
			1.3	2.1	James U. Jackson Memorial Bridge	Crossing of the Savannah River
			1.4	2.3	Northern end of SR 4 concurrency; Georgia–South Carolina state line; northern terminus of SR 4 and 13th Street; southern terminus of Georgia Avenue
South Carolina	Aiken	North Augusta	2.1	3.4	SC 125 south (East Buena Vista Avenue east) / SC 125 Truck begins / West Buena Vista Avenue west – Public Safety Complex, Riverview Park, Lions Field, Community Center	Southern end of SC 125 Truck concurrency; northern terminus of SC 125 and SC 125 Truck; western terminus of East Buena Vista Avenue; eastern terminus of West Buena Vista Avenue
			2.9	4.7	SC 230 / SC 125 Truck south (Martintown Road) – McCormick	Northern end of SC 125 Truck concurrency
			4.4	7.1	US 25 / SC 121 (Knox Avenue) / Chalet North Road east – Edgefield, Saluda	Northern terminus of US 25 Bus.; western terminus of Chalet North Road; northern end of Georgia Avenue name
1.000 mi = 1.609 km; 1.000 km = 0.621 mi       Concurrency terminus

North Augusta connector route

U.S. Highway 25 Connector (US 25 Conn.) is a 0.550-mile-long (0.885 km) connector route of US 25 that is completely unsigned.^[10] Its entire length is in the southwestern part of Aiken County. Nearly all the highway is in the northern part of North Augusta, with a very brief portion within Belvedere. As its name implies, it serves to connect US 25/SC 121 with Interstate 520 (I-520).

The connector route begins at a dead end. It travels to the west-southwest and immediately has an interchange with I-520 (Palmetto Parkway). Just after this interchange, the highway begins a curve to the northwest and intersects the Palmetto Parkway Trail. A short distance later, it very briefly cuts across part of Belvedere and then meets its northern terminus, an intersection with US 25/SC 121 (Edgefield Road). This intersection is on the North Augusta–Belvedere line.^[11]

Major intersections
The entire route is in Aiken County.

Location	mi[11]	km	Destinations	Notes
North Augusta	0.000	0.000	Dead end	Southern terminus
	0.130	0.209	I-520 (Palmetto Parkway) – Augusta, Columbia, Atlanta	I-520 exit 22
North Augusta–Belvedere line	0.550	0.885	US 25 / SC 121 (Edgefield Road) – North Augusta, Edgefield	Northern terminus
1.000 mi = 1.609 km; 1.000 km = 0.621 mi

North Augusta truck route

Edgefield alternate route

Edgefield business route

Edgefield truck route

U.S. Highway 25 Truck (US 25 Truck) is a 3.980-mile (6.405 km) bypass of Edgefield, South Carolina, along Bauskett Street (S-19-10). Signage in the area shows a business banner on top of US 25, which goes through downtown Edgefield; it is in fact mainline US 25. The truck route is on a secondary road; it may be considered as a viable bypass.^[13]

Greenwood business loop

U.S. Highway 25 Business (US 25 Bus.) is a business route of US 25 in Greenwood, South Carolina, and its western terminus of SC 34 along with US 178.^[15]

Hodges alternate route

Ware Shoals business loop

U.S. Highway 25 Business (US 25 Bus.) is a 4.310-mile (6.936 km) business route of US 25 that is partially within the city limits of Ware Shoals, South Carolina. Most of the highway is within Greenwood County; the rest of it is in Laurens County. The highway also has a concurrency with SC 252.^[18]

Greenville business loop

U.S. Highway 25 Business (US 25 Bus.) was established in 1968 or 1969 when US 25 was rerouted to bypass west of downtown Greenville, South Carolina. US 25 Bus. traveled along Augusta Road, Main Street, College Street, Buncombe Street, Rutherford Street, and Poinsett Highway; in 1975, it was rerouted onto Academy Street, removing it along Main Street. In 1995, it was decommissioned; Over half of the route was already overlapped with a U.S. Highway, while SC 20 and SC 291 were extended on parts of the former highway, leaving only a section of Augusta Road downgraded to secondary roads.^[20]

Greenville–Travelers Rest alternate route

Travelers Rest connector route

U.S. Highway 25 Connector (US 25 Conn.) is an unsigned 1.100 miles (1.770 km) connector route in concurrency with US 276 Conn., along Poinsett Highway. It connects US 25 with US 276, in downtown Travelers Rest, South Carolina.^[22]

Hendersonville business loop

U.S. Highway 25 Business (US 25 Bus.) was established in 2003 when mainline US 25 was rerouted along I-26. Replacing a section of US 176, it traverses through East Flat Rock, downtown Hendersonville, and Mountain Home, North Carolina, before reconnecting with mainline US 25 near Fletcher.

Hendersonville alternate route

U.S. Highway 25A (US 25A) was a one-mile (1.6 km) alternate route in downtown Hendersonville, North Carolina, via Church Street, while mainline US 25 was on Main Street. In the early 1960s, it was renumbered as southbound US 25, with Main Street becoming northbound.

Arden–Asheville alternate route

U.S. Highway 25A (US 25A) was established in 1934 as a renumbering of NC 69; the routing has remained unchanged since. US 25A begins in Arden, North Carolina, at the junction of NC 280 and US 25; travels north to Asheville near Biltmore Estate and junctions back at US 25.

Marshall business loop

U.S. Highway 25 Business (US 25 Bus.) was established in 1960 when mainline US 25 was rerouted along new routing north of Marshall, North Carolina. In complete concurrency with US 70 Bus., it originally traversed along Main Street and Tillery Branch Road; in 1981, it was routed and extended further east along Ivy River Road.

Corbin truck route

Richmond business loop

U.S. Route 25 Business (US 25 Bus.) is a 3.654-mile-long (5.881 km) business loop located in Richmond, Kentucky. It runs along the original alignment of US 25 through downtown Richmond, while US 25 proper bypasses the city to the east. US 25 Bus. is signed concurrently with US 421 Bus. for its entire length, as US 421 also runs concurrent with US 25 through the Richmond area.

Major intersections
The entire route is in Madison County.

Location	mi[27]	km	Destinations	Notes
Richmond	0.000	0.000	US 25 / US 421 (Berea Road / Eastern Bypass) / KY 876 west (Eastern Bypass)	Southern terminus; eastern terminus of KY 876
	1.027	1.653	KY 52 east (East Main Street)	South end of KY 52 overlap
	1.634	2.630	KY 388 north (North Second Street) / South Second Street	Southern terminus of KY 388
	1.780	2.865	KY 52 west (Lancaster Avenue)	North end of KY 52 overlap
	2.081	3.349	KY 169 north (Tates Creek Avenue) / Norwood Drive	Southern terminus of KY 169
​	3.401	5.473	KY 3087 south (Old Lexington Road)	Northern terminus of KY 3087
​	3.654	5.881	US 25 / US 421 (Lexington Road / Dr. Robert R. Martin Bypass) / KY 2875 north (McCord Lane) to I-75	Northern terminus; southern terminus of KY 2875; continues beyond US 25/US 421 as KY 2875
1.000 mi = 1.609 km; 1.000 km = 0.621 mi

Lexington business loop

Lexington truck route

Dry Ridge business loop

U.S. Route 25 Business (US 25 Bus.) is a 2.239-mile-long (3.603 km) business loop located in Dry Ridge, Kentucky. It runs along the original alignment of US 25 through downtown Dry Ridge, while US 25 proper bypasses to the east of Dry Ridge.

Major intersections
The entire route is in Grant County.

Location	mi[27]	km	Destinations	Notes
Williamstown	0.000	0.000	US 25 / KY 22 (North Main Street)	Southern terminus; south end of KY 22 Bus. overlap
	0.345	0.555	KY 3025 south (Arnie Risen Boulevard)	Northern terminus of KY 3025
Dry Ridge	1.309	2.107	KY 2501 north / Stewart Lane	Southern terminus of KY 2501
	2.012	3.238	KY 22 Bus. west (Broadway Street)	North end of KY 22 Bus. overlap
	2.239	3.603	US 25 (Scott Street)	Northern terminus
1.000 mi = 1.609 km; 1.000 km = 0.621 mi

Covington business route

Perrysburg–Toledo business route

Toledo business route

Toledo–Erie alternate route

Michigan