This article relies largely or entirely on a single source. (July 2022)
|Length||715 mi[ citation needed] (1,151 km)|
|Existed||1926[ citation needed]–present|
|West end||US 64 / US 70 / US 79 at Memphis, TN|
|East end||Line Street at Charleston, SC|
|States||Tennessee, Mississippi, Alabama, Georgia, South Carolina|
U.S. Route 78 (US 78) is an east–west United States Numbered Highway that runs for 715 miles (1,151 km) from Memphis, Tennessee, to Charleston, South Carolina. From Byhalia, Mississippi to Birmingham, Alabama, US 78 runs concurrently with Interstate 22 (I-22). The highway's western terminus is at US 64/ US 70/ US 79 (Second Street) in Memphis, and its eastern terminus is on Line Street, in Charleston.
US 78 runs along Linden Avenue, Somerville Street, E. H. Crump Boulevard, and Lamar Avenue through Memphis, Tennessee. In Tennessee, US 78 is historically known as Pigeon Roost Road, and some aborted sections of the highway in Mississippi also claim that name as well as Lamar Avenue. Throughout the Tennessee portion, US 78 is overlapped in its entirety by State Route 278 (SR 278), along Linden Avenue and Somerville Street, and State Route 4 (SR 4) along E. H. Crump Boulevard and Lamar Avenue. 
US 78 is a freeway for its entire length in Mississippi. The section from its intersection with Interstate 269 in Byhalia, Mississippi to the Alabama state line is concurrent with Interstate 22. The highway runs across the northeastern rural part of the state, connecting several population centers. Mississippi's portion of US 78 is defined in Mississippi Code Annotated § 65-3-3. The old routing of US 78 through the state is signed as MS 178.
US 78 is a major east–west U.S. highway across the central part of Alabama. It is internally designated State Route 4 (SR 4) by the Alabama Department of Transportation, though the only section of State Route 4 that is signed is along portions mainly west of Jasper. The section from the Mississippi state line to near Graysville is concurrent with Interstate 22; from Graysville south to Birmingham, US 78 takes its original routing. East of Birmingham to the Georgia state line, US 78 has been replaced as a major through-route by Interstate 20. The two routes roughly parallel each other, with junctions at Leeds and Pell City. 
West of Jasper, old US 78 is signed as AL 118 to Guin, and the segment from Guin northward to I-22 at Hamilton is signed as US 43/US 278.
US 78 enters Georgia in Haralson County, and then proceeds through Carroll County and Douglas County. In Douglasville, located in Douglas County, US 78 runs through the downtown, historical part of the city. It is the original thoroughfare for these Georgia counties.
The route then continues eastward through Cobb and Fulton counties into Atlanta. After crossing Peachtree Street, where US 78 marks a boundary between downtown and Midtown, US 78 is largely conterminous with Ponce de Leon Avenue. As it proceeds due east, this section of the route passes Ponce City Market and crosses the Eastside Trail of the BeltLine before skirting a number of Frederick Law Olmsted-designed parks in the Druid Hills Historic District at the eastern edge of the city.
After entering Decatur in DeKalb County, US 78 departs from Ponce de Leon Avenue to head northeast. South of the site of North DeKalb Mall, another short freeway portion begins — leading from just inside the eastern rim of Interstate 285 (the Perimeter) to the suburbs of Clarkston, Tucker, Stone Mountain, and Snellville. This portion is named the Stone Mountain Freeway, and provides an excellent view of Stone Mountain for eastbound motorists.
The route then proceeds east across Gwinnett, Walton, and Oconee counties. In Oconee County, US 78 leaves Moina Michael Highway at the SR 316 interchange, turning right and running concurrent with SR 316/ US 29. (From this point, Moina Michael Highway is signed as US 78 Business, which follows the original route of US 78 through Athens, Ga.) At the terminal eastern interchange of SR 316 both US 78 and US 29 turn right and join with SR 10 Loop, a mostly interstate-grade bypass that rings Athens-Clarke County. US 78 exits the bypass and turns right at the Lexington Road interchange. From there US 78 passes through Oglethorpe, Wilkes, McDuffie and Columbia Counties into Augusta and then onto one of the twin bridges across the Savannah River into South Carolina. 
US 78 provides the most direct route between Augusta and Charleston, through the South Carolina Lowcountry. Crossing Savannah River into the state, it goes northeast into Aiken before going southeasterly through the cities and towns of Williston, Blackville, Denmark, Bamberg, Branchville, and St. George. East of Dorchester, it parallels Interstate 26 into downtown Charleston, where it ends. 
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In western Alabama, the historical name of US 78 is Bankhead Highway. It is also known by this name in portions of Georgia, including Atlanta, and the Bankhead neighborhood takes its name from that stretch of road. Also, the old section of US 78 (now MS 178) that travels through downtown New Albany, Mississippi, is named Bankhead Street.
Throughout the 2000s, US 78 has been gradually upgraded into a four-lane freeway in Mississippi and Alabama and signed as I-22. US 78 is concurrent with I-22 from Byhalia, Mississippi to just outside of Birmingham, Alabama, only branching off just outside of Graysville, Alabama with I-22 traveling about 11 miles (18 km) eastward to its terminus at I-65. 
US 78 and SR 4 in Memphis, Tennessee is currently being upgraded between the Mississippi state line and SR 176, a distance of about 5.1 miles (8.2 km). The route, Lamar Avenue, sees heavy freight traffic and has "crippling congestion." The work includes expanding the road from four to six lanes, adding three new interchanges, and upgrading additional ones. The work is being done in three segments with the first one starting in 2018.