Gulf of Mexico through Lafayette County

State Road 51 begins in Steinhatchee and throughout Taylor County, it follows the west bank of the Steinhatchee River. Within the community it runs along First Avenue South, Riverside Drive, both of which runs east and west. It then bears left onto Fourth Avenue South, which curves into 15th Street East, where it runs in its intended south-to-north direction for the first time. North of Steinhatchee SR 51 is named St. Linhatchee Drive and winds through the wetlands of southeastern Taylor County. After curving sharply to the northeast, the first truly major intersection is in Tennille, with the triple-overlap of US 19/98/ALT 27, a combination that spans from Chiefland to Perry. SR 51 curves back to the left, but still runs northeast.

The road briefly enters the northwest corner of Dixie County near the Steinhatchee Springs Wildlife Management Area, only to cross over into Lafayette County. Still within the Steinhatchee Springs WMA, the road continues through southwestern Lafayette County, but suddenly starts to curve more to the east as it approaches the northern terminus of County Road 357 in Cooks Hammock. Continuing to curve to the east and move away from the southwestern portion of the county it crosses over the Steinhatchee River, but then starts to curve more northerly again, and even to the northwest before it approaches the western terminus of CR 360. The road curves back to the northeast and finally straightens out as it enters the Town of Mayo and becomes Fletcher Avenue. One other county road terminates at SR 51 in the town, specifically CR 355 which continues west as Pine Street. The much more important intersection is at the center of town which happens to be U.S. Route 27 (West Main Street and East Man Street). From there it runs between Lafayette County Courthouse (Florida) which occupies the entire block between US 27 and Bloxham Street, and across the street the Old Mayo Free Press Building next door to the Old Lafayette County Courthouse which can be found on the southeast corner of SR 51 and Bloxham Street. The last county road in town is CR 400. Further north it intersects CR 534, and a block later it runs into the last routed intersection in Lafayette County which is CR 354 (South Convict Spring Road), but the last intersection in the county at large is with a cul-de-sac named Northeast Castagna Lane. North of there the road crosses the historic Hal W. Adams Bridge over the Suwannee River.

Suwannee County to Georgia State Line

As it crosses the Suwannee County Line, the road is given the name Irvin Avenue Northwest, a name it keeps throughout much of the county. Within Luraville it remains relatively straight at first as it passes through the Peacock Springs State Recreational Area, but starts to curve northeast, where it intersects the western terminus of CR 252, the northern terminus of CR 349, and the eastern terminus of CR 250. As it enters the historic City of Live Oak the road is named Irvin Avenue Southwest and continues to run at the same northeast to southwest angle. This trajectory end at 11th Street where CR 136 officially joins SR 51 in an overlap, however both are overshadowed by US 129 (South Ohio Avenue). It is at this point both routes turn left onto Ohio Avenue. Roughly two blocks later, the road encounters CR 10A (Helvenston Street Southeast). Further downtown it becomes the location for the Old Live Oak Post Office, and later, the Suwannee County Courthouse, and then the four corners of the city at U.S. Route 90 (hidden SR 10), where US 129/SR 51's name changes from South Ohio Avenue to North Ohio Avenue, and US 90's name changes from West Howard Street to East Howard Street.

One block later it crosses the railroad tracks where the historic Union Depot and Atlantic Coast Line Freight Station can be found, and the Old Live Oak City Hall can be found on the next block. It is here where the multiplex with State Road 136 ends at West Duval Street Northeast. After leaving the city limits, the road eventually becomes a four-lane divided highway as it approaches Interstate 10 at Exit 283, only to revert to a two-lane undivided road after it passes under the interchange. The only other intersection from here is CR 136A. The road enters Suwannee Springs, Florida, where it meets the intersection with CR 132, and secretly takes it north, as it prepares to make a second crossing over the Suwannee River. At this point it winds around another former bridge that carried SR 51, and eventually US 129 onto a much newer bridge, curving left and then right over the river as it enters Hamilton County.

Unlike in Suwannee County, only a hint of the right-of-way of the former segment of US 129 can be found before the road turns straight north before letting go of its multiplex with CR 132, which runs east. Further north it enters the unincorporated community of Marion, where it intersects one other county road before meeting another interchange, this time Interstate 75 at Exit 451 Beyond that, it passes through Hillcoat, where US 129/SR 51 joins US 41 as well as hidden SRs 25 and 100. The newly overlapped routes briefly run straight north before making a reverse curve around the left side of Roberts Pond and Shaky Pond before entering the City of Jasper. US 41/129/SR 100 turns west onto State Road 6 (Hatley Street), which becomes County Road 6 east of the intersection, while County Road 51 (First Avenue Northeast) begins one block to the west.

CR 51 runs briefly along First Avenue Northeast to Second Street Northeast, where it turns right, only to curve northeast again. Shortly after the curve, it has an at-grade crossing with a Georgia Southern and Florida Railway line that was following US 41 since Lake City. At Northeast 39th Drive, the road curves more northerly, although not necessarily straight north. The road winds through local Northern Florida forest land with occasional wetlands even as it passes through the barely existing community of Bakers Mill. After crossing a narrow bridge over the Little Alapaha River it intersects a dirt road named Northwest 13th Street which leads to US 129 near Avoca. The rest of the journey of CR 51 is surrounded by scrub forest. County Road 51 runs north to the Georgia border at a T intersection with two dirt roads named Flaline Break Road and Barnes Road, the latter of which is entirely dirt as far north as its terminus with State Route 94 at Tarver, Georgia.