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Several special routes of U.S. Route 25 exist. In order from south to north they are as follows.
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Statesboro bypass
U.S. Route 25 Bypass (US 25 Bypass), in complete concurrency with SR 67 Bypass, is the western half of the divided four-lane bypass, west around Statesboro, Georgia also known as "Veterans Memorial Parkway." The eastern half is U.S. Route 301 Bypass (Statesboro, Georgia), which is in concurrency with Georgia State Route 73 Bypass.
Waynesboro bypass
U.S. Route 25 Bypass (US 25 Bypass), in complete concurrency with SR 121 Bypass, is a divided four-lane bypass, west around Waynesboro, Georgia.
Edgefield truck route
U.S. Route 25 Truck (US 25 Truck) is a 3.9-mile (6.3 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. Visitors may consider the truck route as a viable bypass.
Greenwood business loop
U.S. Route 25 Business is a business route of U.S. Route 25 in Greenwood and its western terminus of SC 34 along with US 178.
Travelers Rest connector
U.S. Route 25 Connector (US 25 Conn) is an unsigned 1.0 mile (1.6 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.
Hendersonville business loop
U.S. Route 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.
Asheville alternate route
U.S. Route 25 Alternate (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 the Biltmore Estate and junctions back at US 25.
Marshall business loop
U.S. Route 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.
Greenville business loop
U.S. Route 25 Business (US 25 Bus) was established in 1968 or 1969 when US 25 was rerouted to bypass west of downtown Greenville. US 25 Bus traveled along Augusta Road, Main Street, College Street, Buncombe 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. Route, 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.
Hendersonville alternate route
U.S. Route 25 Alternate (US 25A) was a 1.0-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.