US 278 begins at an intersection with US 59/US 71 in the town of Wickes in southwestern Arkansas.[1] From Wickes, US 278 continues eastward near Gillham Lake to an overlap with US 70 through Dierks.[2] Continuing south, US 278 overlaps Highway 26 for 0.09 miles (0.14 km) at Center Point.[3] Further south the route continues into Nashville. The route overlaps US 371 and later Highway 27 upon entering Nashville.
Entering Hempstead County, the highway winds through rural areas to Ozan and Washington, before meeting US 278 Business (US 278B) outside Hope.[4] The highway crosses over Interstate 30 (I-30) shortly after entering the city limits and overlaps Highway 29 and Highway 32. US 278/AR 29/AR 32 intersect US 67 in east Hope. South of this junction AR 29 splits and US 278/AR 32 continues southeast. Further along this route, AR 32 turns southeast to Willisville and US 278 runs toward Camden.
The route intersects Highway 53 in rural Nevada County, overlaps US 371 in Rosston, and has a junction with Highway 57 upon entering Ouachita County.[5][6] In Camden, US 278 intersects Highway 24 before it meets US 278B and US 79B prior to overlapping US 79. US 278 breaks from US 79 near Harrell Field shortly before entering East Camden. US 278 continues into Calhoun County and Hampton and a junction with US 371.[7] The east edge of town brings an intersection with Highway 274 as US 278 continues to Harrell and Highway 160 before entering Bradley County. Aside from Banks, where US 278 has a junction with Highway 275, the route runs through rural country until Warren, where US 278 almost entirely bypasses the city to the south while US 278B runs downtown, including a brief overlap with US 63B. US 278 has an intersection with US 63/AR 8 along the southern edge of Warren before serving as the eastern terminus for US 278B. Further east the highway intersects Highway 172, which gives access to the Warren Prairie Natural Area just east of the Drew County line.[8]
The route continues to Monticello to McGehee, where it meets US 65. US 278 overlaps US 65 southward for 16 miles (26 km) until they separate in Lake Village. There, US 65 splits off and US 278 overlaps US 82 east to the Mississippi River, where US 82/US 278 crosses into Mississippi.
Long-term plans are to move US 278 to the Charles W. Dean Bridge,[9] which is part of the proposed extension of I-69.
US 278 enters Alabama between Greenwood Springs, Mississippi, and Sulligent, Alabama. As in Georgia, this and all U.S routes are partnered with state routes; however, there are few instances throughout the state where the state route number is posted. From the Mississippi state line to Guin, US 278 is paired with State Route 118. From Hamilton to the Georgia state line, US 278 is paired with State Route 74.
US 278 junctions with US 431 at Gadsden. The two routes overlap until they split at Attalla. US 278 overlaps US 43 between Hamilton and Guin. Prior to the completion of Corridor X (Future I-22), these two routes also overlapped US 78 between these two towns; eastbound US 78 traveled in the same direction as westbound US 278.
In Atlanta, US 278 runs along Donald Lee Hollowell Parkway (Bankhead Highway), North Avenue, briefly along Piedmont Road and Ponce de Leon Avenue. Outside the Perimeter, US 278 runs along Covington Highway. In Lithonia, Georgia, at the intersection with Turner Hill Road (SR 124), US 278 merges with I-20 for 15 miles (24 km). It leaves I-20 at exit 90, in Covington, Georgia.
US 278 is co-signed with a state route for its entire length in Georgia, as are all U.S. Highways in the state. From the Alabama line into Lithia Springs, it is co-signed with SR 6. From Lithia Springs through Atlanta, it is merged with US 78/SR 8. In Atlanta, US 278 merges further with other highways including SR 10 and US 23 before splitting off at Ponce de Leon Ave. and East Lake Road near Decatur. In Avondale Estates, SR 12 is paired with US 278, all the way into Thomson. There, US 278 merges with US 78/SR 10 to the South Carolina line.
Upon reaching Hardeeville, the route heads eastward toward the Atlantic with major new developments lining the spine of the road from Hardeeville through Sun City and Bluffton before crossing over the bridge to Hilton Head Island. US 278 ends at US 278 Business on the southern portion of Hilton Head Island, just outside Sea Pines Plantation.
Alabama rerouted a section of US 278 in Guin over a section of SR 118 in 1995. At the same time, South Carolina rerouted the highway in Ridgeland over US 17 and SC 88.[15]
Alabama relocated US 278 in Gadsden in 2000.[18] Until early 2005, US 278 was only signed in Mississippi from the Alabama state line to US 45 west of Amory. US 278 in western Alabama was formerly routed through Haleyville via current SR 195 and SR 129.[citation needed] In 2014, Alabama relocated US 278 in Cullman.[19]
^Planning and Research Division (2000). General Highway Map, Polk County, Arkansas(PDF) (Map). 1:62,500. Arkansas State Highway and Transportation Department. Archived from the original(PDF) on March 13, 2012. Retrieved December 28, 2011.
^Planning and Research Division (2000). General Highway Map, Howard County, Arkansas(PDF) (Map). 1:62,500. Arkansas State Highway and Transportation Department. Archived from the original(PDF) on March 13, 2012. Retrieved December 28, 2011.
^Planning and Research Division (2000). General Highway Map, Hempstead County, Arkansas(PDF) (Map). 1:62,500. Arkansas State Highway and Transportation Department. Archived from the original(PDF) on July 18, 2011. Retrieved December 28, 2011.
^Planning and Research Division (2011). General Highway Map, Nevada County, Arkansas(PDF) (Map). 1:62,500. Arkansas State Highway and Transportation Department. Archived from the original(PDF) on July 18, 2011. Retrieved December 31, 2011.
^Planning and Research Division (2008). General Highway Map, Ouachita County, Arkansas(PDF) (Map). 1:62,500. Arkansas State Highway and Transportation Department. Archived from the original(PDF) on September 23, 2015. Retrieved December 31, 2011.
^Planning and Research Division (1999). General Highway Map, Calhoun County, Arkansas(PDF) (Map). 1:62,500. Arkansas State Highway and Transportation Department. Archived from the original(PDF) on January 27, 2021. Retrieved January 9, 2012.
^Planning and Research Division (2008). General Highway Map, Bradley County, Arkansas(PDF) (Map). 1:62,500. Arkansas State Highway and Transportation Department. Retrieved January 9, 2012.
^"Minutes of the Meeting of the Arkansas State Highway Commission, August 6, 1997"(PDF). p. 963. Archived from the original(PDF) on July 21, 2019. Retrieved March 3, 2015. WHEREAS, the State of Mississippi has expressed interest in extending U.S. 278, which presently ends at Tupelo, westward into Arkansas on a temporary location, utilizing the U.S. 82 river crossing, with an ultimate alignment over the future Great River Bridge and connecting roadways;
^Special Committee on U.S. Route Numbering (May 29, 2014). "Report to SCOH" (Report). Washington, DC: American Association of State Highway and Transportation Officials. Archived from the original(DOCX) on February 26, 2020. Retrieved June 3, 2022.
^Rand McNally (2014). The Road Atlas (Walmart ed.). Chicago: Rand McNally. pp. 4, 10–11, 28, 56, 92. ISBN978-0-528-00771-2.