Interstate 95 (I-95) is a major Interstate Highway, running along the East Coast of the United States from Florida to Maine. In South Carolina, I-95 runs approximately parallel to the Atlantic Ocean shore although about 50 miles (80 km) inland, from Hardeeville in the south to Dillon in the northeast. The route runs through the cities of Florence and Walterboro.

For the most part, the 199-mile (320 km) drive is fairly benign, passing through the pine forests, farmlands, and blackwater streams and swamps of the Atlantic Plain. As the route travels north, it moves inland from coastal cities such as Hardeeville and inland to cities such as Darlington. However, a few landmarks do exist to break up the monotony. Crossing from the south from Georgia just over the Savannah River bridge, motorists are greeted to an elaborate gateway of sabal palmettos into the state of South Carolina. The Juanita M. White Crosswalk also exists between exits 18 and 21. A flyover on twin high-spans over Lake Marion provides an unexpected scenic break in the center of the highway's length. The old US Highway 15 (US 15)/US 301 bridge runs along the west side of I-95 and is used for recreational purposes. Moving further north and out of the Palmetto State, the North Carolina state line is prominently marked by the South of the Border amusement complex at the US 301/US 501 exit. Local traffic parallel to the Interstate uses a combination of US 17 and US 17 Alternate (US 17 Alt.) from the Georgia state line north of Savannah to Walterboro, US 15 from Walterboro to Santee, and US 301 from Santee to South of the Border. In addition, I-95 shares a number of concurrencies, or multiplexes, with three of these US Highways at various stretches in South Carolina.

The South Carolina Department of Transportation (SCDOT) operates and maintains three welcome centers and five rest areas along I-95. Welcome centers, which have a travel information facility on site, are located at milemarkers 4 (northbound), 99 (southbound), and 195 (southbound); rest areas are located at milemarkers 47 (north and southbound), 99 (northbound), and 139 (north and southbound). Common at all locations are public restrooms, public telephones, vending machines, picnic areas, and barbecue grills.

The South Carolina Department of Public Safety (SCDPS) and South Carolina State Transport Police (STP) operate and maintain one truck inspection/weigh station, located northbound at milemarker 74. The location utilizes weigh-in-motion that does not require commercial motor vehicles to leave the freeway to be weighed. An inspection shed and pit are also on site, where full-service inspections are performed for flagged and randomly picked trucks.

Several parking area locations are also found along I-95; these were either formally rest areas or weigh stations that were converted. The parking areas offer no amenities and some are even restricted for commercial motor vehicles only.

I-95 in South Carolina feature numerous dedicated or memorialized bridges, interchanges, and stretches of freeway.

I-95 first appeared on state maps between 1962 and 1964, with construction from US 17 north of Hardeeville to Ridgeland. By 1967, more sections were under construction, including Pocotaligo to Walterboro and Santee to the North Carolina state line. The first section to officially open happened in 1968, from South Carolina Highway 527 (SC 527), near Gable, to SC 9/SC 57, in Dillon.

In 1971–1972, more sections of I-95 was completed: going north from SC 9/SC 57, in Dillon, to the North Carolina state line and going south from SC 527, near Gable, along the recently completed 1968-built Lake Marion bridge, to the US 301 connector, in Santee (exit 97). Also part of US 17 between Ridgeland (exit 22) to near Yemassee (exit 33) was combined with I-95, with temporary status through Coosawhatchie; I-95 then continued on new freeway north to SC 63, in Walterboro.