U.S. 378 travels 209 miles east from the Savannah River Bridge spanning Clark Hill Lake on the Georgia state line to U.S. 501 Business (Main Street) in Conway. U.S. 378 connects the county seats of McCormick, Saluda and Lexington in western South Carolina. Heading east across the Columbia metropolitan area, U.S. 378 overlaps with U.S. 1 in Lexington, and again from West Columbia across the Gervais Street Bridge into the capital city.
U.S. 76 joins U.S. 1/378 along Gervais Street east from Bull Street. U.S. 1 turns north onto Millwood Avenue while U.S. 76/378 shift southeast onto Millwood Avenue and Devine Street by the Rosewood neighborhood in Columbia. U.S. 76/378 continue along Garners Ferry Road to I-77, Horrell Hill and the Sumter County line over the Wateree River.
U.S. 76/378 overlap east onto a freeway bypass around the north side of Sumter. The two split on the east side of hte city for Mayesville and Turbeville respectively. U.S. 378 overlaps with U.S. 301 for 0.72 miles along Main Street in Turbeville and straddles the Florence County line east toward Lake City. A 4.49 mile long business route loops south into Lake City along a combination of Main Street, Church Street and Myrtle Beach Highway.
Traversing rural areas and wetlands, U.S. 378 continues east from Lake City to southern Marion County across the Pee Dee River. U.S. 378 spans the Little Pee Dee River to Little Pee Dee Swamp in Horry County. Wright Boulevard leads U.S. 378 southeast into the city of Conway. The route concludes along 3rd Avenue, one block south of S.C. 905 in Downtown.
West
N Mathews Road (Road 278) intersects U.S. 378 west of the exchange with U.S. 52 on the north side of Lake City.
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U.S. 378 (Turbeville Highway) straddles the Clarendon / Florence County line west to Scurry Road (Road 972) north.
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South West
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U.S. 378 shifts off Myrtle Beach Highway northwest at S.C. 763 onto the Robert E. Graham Freeway bypassing Sumter.
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S.C. 763 extends Myrtle Beach Highway west 2.20 miles to U.S. 76 Business (Liberty Street) en route to Downtown Sumter.
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U.S. 76 (Florence Highway) west converges with U.S. 378 and U.S. 76 Business (Liberty Street) at a parclo interchange.
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The business route for U.S. 76 through Sumter loops 5.91 miles across the city.
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U.S. 76 accompanies U.S. 378 (Robert E. Graham Freeway) westbound ahead of a modified diamond interchange with U.S. 401 (Oswego Highway).
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West
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U.S. 401 originates in Downtown Sumter at the intersection with U.S. 76 Business and U.S. 521 at Calhoun and Washington Streets.
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U.S. 15 overtakes N Main Street from Lafayette Drive ahead of the grade separation with U.S. 76/378 (Robert E. Graham Freeway).
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U.S. 15 travels north from Sumter to the Lee County seat of Bishopville, Hartsville and Bennettsville.
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Right in right out (RIRO) ramps link U.S. 76/378 with N/S Pike West, service roads connecting with U.S. 15 (N Main Street).
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U.S. 76 Business/521 (Broad Street) combine northwest from Downtown Sumter along Broad Street and separate just south of U.S. 76/378.
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U.S. 521 continues northwest from Sumter to the Kershaw County seat of Camden, Lancaster and Charlotte, North Carolina.
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A half diamond interchange joins U.S. 76/378 with U.S. 521 (Camden Highway).
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U.S. 76/378 overtake Broad Street from the Robert E. Graham Freeway and west end of U.S. 76 Business.
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The succeeding intersection along U.S. 76/378 is with S.C. 120 south along Alice Drive.
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West
U.S. 378 (Sunset Boulevard) meets Interstate 20 at a six-ramp parclo interchange (Exit 61) midway between West Columbia and Lexington.
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Corley Mill Road (Road 68) arcs 5.08 miles northwest from U.S. 378 (Sunset Boulevard) to S.C. 6 (Lake Drive) by Lake Murray Dam.
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Lexington Marketplace shopping center was constructed on the north side of U.S. 378 at Palmetto Park Boulevard in 2016/17.
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West 
South
S.C. 6 combines with U.S. 378 along N Lake Drive for 0.29 miles. The arterial intersects Northwood Road (Road 392) west at Abbie Lane east.
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S.C. 6 continues south along Lake Drive to U.S. 1 in Downtown Lexington. U.S. 378 turns west along Columbia Avenue through a commercial strip.
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West
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U.S. 1 (Main Street) heads northwest to join U.S. 378 (Columbia Avenue) west at Old Chapin Road (Road 52).
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U.S. 1/378 overlap 0.67 miles west to Gibson Road (Road 176). The two previously ran concurrent between Columbia and West Columbia.
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South West 
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U.S. 378 diverges from U.S. 1 (Main Street) to the north as both proceed through the suburban areas outside the town of Lexington.
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U.S. 1 continues west from Lexington to Batesburg-Leesville while U.S. 378 reaches Saluda in 30.6 miles.
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West
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U.S. 378 crosses the Beaverdam Creek arm of Lake Murray over Jake Knott's Bridge.
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The four lane section of U.S. 378 concludes west of Beulah Church and Priceville Roads (Road 24).
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Construction from 2017 to December 15, 2020 replaced bridges along U.S. 378 over both Horse Creek and Hollow Creek at Lake Murray.
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West
Reassurance marker posted west of McNeary Ferry Road (Road 138).
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S.C. 391 converges with U.S. 378 (Columbia Highway) at a traffic rotary.
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S.C. 391 follows Summerland Highway north from Batesburg-Leesville to U.S. 378.
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S.C. 391 continues north from U.S. 378 along Prosperity Highway toward the town of Prosperity in Newberry County.
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U.S. 378 (Columbia Highway) west of Double Bridges Road (Road 26).
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U.S. 378 (Travis Avenue) meets the west end of S.C. 194 (Jennings Highway) at U.S. 178 Connector in Saluda.
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Travis Avenue extends 0.19 miles west from U.S. 378 as U.S. 178 Connector to U.S. 178 and S.C. 121 at N Main Street.
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S.C. 194 runs 14.69 miles northeast to S.C. 391 near Lake Murray.
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Jennings Street leads U.S. 378 three blocks south from S.C. 194 to E Church Street and Downtown Saluda.
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Atlanta, Georgia appears on a distance sign where U.S. 378 turns onto Church Street. This takes into account U.S. 378 to Washington, Georgia and U.S. 78 west from there.
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U.S. 178/S.C. 39-121 combine along Main Street through Downtown Saluda.
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S.C. 67 (Callison Highway) stems 14.30 miles north from U.S. 378 to U.S. 25/178 near Greenwood.
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Walker Road (Road 35) extends 8.83 miles southeast from U.S. 378/S.C. 67 to S.C. 283 (Plum Branch Road).
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15.60 miles remain along U.S. 378 west in South Carolina across McCormick County.
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U.S. 378 (E Gold Street) and U.S. 221 (Greenwood Highway) combine just north of the McCormick street grid.
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South West
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U.S. 221/378 (Gold Street) south at Main Street in Downtown McCormick.
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U.S. 221 splits with U.S. 378 west to join S.C. 28 south at Mine Street.
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West
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A new bridge for U.S. 378 across the Savannah River was completed in 2016.
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The mid point of the Savannah River marks the Lincoln County, Georgia line along U.S. 378 west.
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Connect with:
Interstate 20
Interstate 26
Interstate 95
U.S. 1
U.S. 15
U.S. 21
U.S. 25
U.S. 76
U.S. 78
U.S. 176
U.S. 178
U.S. 301
U.S. 321
U.S. 601
Page Updated 09-24-2021.