The northernmost of SR 100 are signed (north–south) as
US 129. For in
Jasper, it merges with
US 41 (hidden
SR 25) before separating from US 129 (which has the hidden
Florida Department of Transportation designation
SR 51 between the split and
Live Oak). The overlap with US 41 terminates in
Lake City, when it turns east onto
US 90 (hidden
SR 10), which is also joined by another hidden overlap with
SR 47 until that route turns north at the intersection with
US 441 (hidden
SR 25A). 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. East of the intersection of Union County Road 100A, SR 100 crosses over a bridge over Swift Creek, but doesn't cross any county or other municipal borders. Only after the intersection with Union County Road 231 does the road enter the city limits of
Lake Butler where it encounters the eastern terminus of
Florida State Road 238 and the western terminus of the
Palatka-Lake Butler State Trail. Curving away from the trail, the route passes through downtown Lake Butler. After the intersection with
SR 121, SR 100 leaves the Lake Butler city limits. The route encounters the bridge over Richland Creek but remains in Union County until it reaches the bridge across the
New River, where it crosses the Union-Bradford county line. Just under 12 miles later, the road enters
Starke, where it encounters an interchange with US Alternate 301,
the truck bypass around the city. After the interchange SR 100 adopts the name Madison Street. SR 100 runs straight west to east along Madison until Orange Street, where it resumes its original southwest to northeast trajectory through the intersection with mainline
US 301 (Temple Avenue /
SR 200). Beyond US 301, SR 100 forms the southern border of the
Call Street Historic District. The route climbs a bridge over the CSX
Wildwood Subdivision, and them make a sharp right turn towards the south-southeast direction. Along the way it passes through the rural community of
Theressa, where it intersects Bradford County Road 18, an eastern county extension of
SR 18. SR 100 secretly takes CR 18 with it in an overlap, then lets the county road branch out on its own again south of the road to
Keystone Heights Airport. The road briefly curves to the southwest momentarily crossing the Palatka-Lake Butler State Trail just before curving back to the southeast as it crosses the Bradford-Clay county line and enters
Keystone Heights. Even within the semi-urban surroundings of the city, the closest resemblance to a major intersection in Keystone Heights is
SR 21. The route begins curving away from the trail before entering
Lake Geneva. 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. CR 214 breaks away from the overlap east of where the routes leave Lake Geneva and enter
Melrose. The last intersection with a route designation in Clay County, is Clay CR 219. and the last intersection in Clay County at large is with the historic
Old Bellamy Road at the Clay-Putnam County Line The trail returns to the north side of the road just before the intersection with Forest Hills Road in
Putnam Hall where the road serves as the eastern terminus of
SR 26. 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. It also passes through the
Rice Creek Conservation Area before entering
Springside, where it intersects CR 309D and then 309C. Between these two intersections, SR 100 gains the street name Reid Street. One last trailhead for the state trail is encountered on the north side before the south side is flanked by the
Palatka Municipal Airport where the route officially enters the
City of Palatka, just before the intersection with CR 216, which is also where the trail finally comes to an end. The first major intersection in the city is with
SR 19, which is where the route also acquires the
Truck Route for Florida State Road 20. 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. FDOT officially claims that SR 20 runs in a concurrency with SR 100 until the northern terminus of the overlap with US 1 in
Bunnell, but no reassurance signs for that route can be found along this segment. Either way, the route passes
Larimer Arts Center and Riverfront Park just west of
the bridge crossing at
St. Johns River. After the bridge, US 17-SR 100 curves more towards the south at the intersection with
SR 207. 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. The road crosses the Putnam-Flagler County Line without any signage, and continues in a more easterly direction through
Andalusia (formerly
Shell Bluff),
Bimini, and
Bunnell, where SR 100 overlaps
U.S. Route 1 (
SR 5) for a mile. At the northern terminus of
SR 11, SR 100 breaks away from the overlap with US 1 and passes by the
Flagler Executive Airport and Flagler Executive Seaport. Along the property of this airport the route enters the southern reaches of
Palm Coast. 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. After the interstate, SR 100 will pass under an A-Framed Footbridge under construction for the proposed Bulow Trail and Bulow Creek Headwaters Park. 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 three blocks later at
SR A1A on the Atlantic coast. ==Major intersections==