US 17 begins a long concurrency with US 92 just north of Winter Haven in Lake Alfred (US 92 following eastbound), which takes both highways through Kissimmee, where they join US 192.

At the South Carolina state line, US 17 crosses the Savannah River on the Talmadge Memorial Bridge.

At Point South, US 17 leaves I-95 and heads eastward into northern Beaufort County, sharing a concurrency with US 21 until Gardens Corner.

Once in Jacksonboro, the road enters Charleston County, crossing the Edisto River and maintains a four-lane configuration for the remainder of the state.

From the drawbridges, it is known as the Septima Clark Crosstown Connector and is mostly routed north of the affluent historical areas of the city.

Upon reaching the I-26 terminus, US 17 becomes limited-access and above grade as it approaches the Cooper River via the Arthur Ravenel Jr. Bridge.

[citation needed] Upon crossing the river, the highway enters Mount Pleasant at grade and is signalized for several miles up through the second interchange with I-526 and connecting roads to the Isle of Palms and Sullivan's Island.

The road leaves the Charleston metro area and enters the Francis Marion National Forest[2] and going through the rural communities of Awendaw and McClellanville, where Hurricane Hugo made landfall in September 1989.

In Wilmington, US 17 (here concurrent with I-140) crosses the Northeast Cape Fear River between New Hanover and Brunswick counties over the Dan Cameron Bridge.

Between New Bern and James City, US 17 (concurrent with US 70 and North Carolina Highway 55, or NC 55) crosses the Trent River by way of the Freedom Memorial Bridge.

At Morgan's Corner, the US 158 concurrency ends, and US 17 crosses the Pasquotank River into Camden County before heading north into Virginia.

Highways by the Florida Department of Transportation was stopped when the state could only use federal funding for stock black-and-white; a few yellow US 17 signs remain.

[4] US 17 also ran through downtown Myrtle Beach before the new bypass route was finished in the early 1980’s to alleviate heavy traffic.

US 17 Alternate was commissioned as a route between Point South and Georgetown, mostly for trucks who wished to bypass Charleston and the weight restrictions of the former bridges.