East of Lake City, SR 100 is signed east–west as it continues along a northwest–southeast pathway toward the Atlantic Ocean, running along the southern border of the Lake City Gateway Airport, then passing through the community of Lulu, and later crossing the bridge over the Olustee Creek, and thus crossing the Columbia-Union county line.

An intersection with 5th Street leads to the boat ramp to the namesake of the community, and it shared by the western terminus of the hidden overlap with Clay CR 214.

The road and the trail separate from each other again, as they pass through the hills, lakes and former sand mines but returns again within the communities such as Grandin and Florahome.

Straying from the trail one more time, SR 100 curves more to the southeast as it passes by Q. I. Roberts Jr-Sr High School across from the intersection with Holloway Road, which serves as an entrance to Etoniah Creek State Forest.

East of the school, the trail rejoins SR 100 and remains along the north side as they both pass through the barely existing communities of Baywood and Carraway.

From there the road remains relatively in the same direction, mostly surrounded by commercial zoning until it curves more towards the southeast before merging with US 17 (hidden SR 15), taking Reid Street along for the ride.

Together, US 17-SR 100-Truck Route 20 crosses the CSX Sanford Subdivision and the Old Atlantic Coast Line Union Depot which is used as the Amtrak station, and a local railroad museum.

Less than a block after passing an abandoned church, motorists will approach North 9th Street, where the routes encounter SR 20.

Either way, the route passes Larimer Arts Center and Riverfront Park just west of the bridge crossing at St. Johns River.

State Road 100 separates from US 17 in San Mateo and passes along the east side of the Dunns Creek Wildlife Management Area (SJRWMD property) and Crescent Lake.

Sparse development can be found along this segment including the AdventHealth Palm Coast Hospital just before encountering the interchange with Interstate 95 at Exit 284.

[4] Development is spotted along the road again, as the route heads for the bridge over the Matanzas River (Intracoastal Waterway), passing over the Flagship Harbor Preserve and Betty Steflik Park before entering Flagler Beach and terminating thee blocks later at SR A1A on the Atlantic coast.

From Orange Avenue it continues straight west until after it crosses a bridge over a tributary to Alligator Creek, where it leaves the city limits and approaches another railroad line that terminates at the CSX Wildwood Subdivision, and then curves to the southwest.