In the U.S. state of South Carolina, U.S. Route 17 (US 17) is a north–south highway located near the Atlantic Ocean. The route enters the state from Georgia at the Savannah River and serves Charleston and Myrtle Beach before entering North Carolina near Calabash.

US 17 enters into South Carolina in Jasper County as a two-lane road and within eight miles (13 km) enters Hardeeville, where it becomes a major four-lane Freeway configuration. US 17 intersects Interstate 95 at Exit 5 in Hardeeville and after the intersection with US 321, runs parallel to Interstate 95 until Ridgeland, where it merges with the interstate at Exit 22 until Point South. At Point South, US 17 leaves I-95 at Exit 33 and heads eastward into northern Beaufort County, sharing a concurrency with U.S. 21 until Gardens Corner. US 21 splits off to Beaufort while US 17 heads northeast into the ACE Basin and Colleton County.

The stretch of US 17 between Gardens Corner and Jacksonboro is a scenic yet rural two-lane road configuration that has proven to be a very dangerous and deadly stretch for motorists. SCDoT is working on improving portions of the roadway, including widening some portions and reducing the speed limits. Once in Jacksonboro, the road enters into Charleston County crossing over the Edisto River and regaining a four-lane configuration for the remainder of the state. The road passes through several rural communities as it approaches Charleston from the west. Just before the interchange with Interstate 526, major commercial development starts and continues into the West Ashley neighborhood of Charleston until the Ashley River.

In Charleston, US 17 traverses the Ashley River Drawbridges and comes onto the Charleston Peninsula, being routed north of the historical areas of the city. The first portion is at-grade and has a few traffic-signals for flow purposes. Upon reaching the Interstate 26 terminus, US 17 becomes limited-access and above grade as it approaches the Cooper River via the Arthur Ravenel Jr. Bridge and the stretch of US 17 in Charleston is infamous among locals for its traffic congestion, especially on weekday mornings. The 3.6-mile (5.8 km) section running from S.C. Highway 171 to Sam Rittenberg Boulevard has been named the "Charleston Nine Memorial Highway", in honor of nine Charleston firefighters killed in the line of duty in the Charleston Sofa Super Store fire on June 18, 2007.

Upon crossing the river, the highway enters Mount Pleasant at grade and is signalized for several miles up through the second interchange with Interstate 526 and connecting roads to the Isle of Palms and Sullivan's Island. The road leaves the Charleston metro area by entering into the Francis Marion National Forest and going through the rural communities of Awendaw and McClellanville on its northeastern journey to Georgetown. US 17 makes a spectacular crossing of the marsh-lined Santee River as it enters Georgetown County. After going around the charming city of Georgetown, US 17 crosses eastward over the Waccamaw / Pee Dee river system before making a northward turn along the Grand Strand.

The last component of US 17 runs close to the Atlantic, beginning at the Hobcaw Baronry and DeBordieu, passing by Pawleys Island and going around Litchfield Beach. It then enters into Horry County and passing Surfside Beach, Murrells Inlet and arriving in Myrtle Beach. US 17 splits here between a business route and the standard route, which remains west of the beach and tourist areas served by Business 17. The roads rejoin north of the city and continue as US 17 through Atlantic Beach, North Myrtle Beach, and Little River before crossing into North Carolina. The portions from Murrells Inlet to the state line are quite congested at times, though the soon to be constructed Interstate 73 should assist in alleviating many traffic issues.

The route was part of the 1926 approved plan for a national system of highways, and appears on the approved map. When first signed, US 17 followed a route that went through Florence and Marion. The original route through South Carolina was 288 miles (463 km) long.

At this time, U.S. routes in South Carolina used a dual-numbering system; US Route 17 was also signed SC 1 from Georgia to Yemasse, SC 30 from Yemassee to Walterboro, SC 6 from Walterboro to Charleston, SC 2 from Charleston to Goose Creek, SC 41 from Goose Creek to Florence, SC 3 from Florence to North Carolina. By 1928, all of the dual numbers had been removed except for SC 2. The entire route from Georgia to North Carolina was paved by 1930. At one point the route from Green Pond to Jacksonboro was SC 32.

The early routing was already identified to be shifted to the Kings Highway which would pass through Myrtle Beach and Georgetown. The re-routing occurred in 1935.

The first tourist welcome center in South Carolina opened in February 1968 on US 17 near Little River.

US 17 Alt is an alternate route of U.S. Route 17 in South Carolina was created in either 1951 or 1952, as a replacement for mainline U.S. 17 Alt. that runs from Pocotaligo to Georgetown and three other state highways between Walterboro and Georgetown. It is 123.4 miles (198.6 km) long and has been four-laned in various segments since 1970.

US 17 Bus. also known as Kings Highway is a 22.9 mile (36.85 km) business route of U.S. Route 17. From the parent route that runs from Murrells Inlet north to Briarcliffe Acres. Traveling southbound, it connects with the bypass route at the Horry/Georgetown county lines; the business route continues along the waterfront of Murrells Inlet until rejoining the mainline route near Garden City. The road is also a major route during the Bi-Lo marathon weekend; miles 9-12 and also 20-24 run through this highway during the marathon.