U.S. Highway 19 (US 19) runs about 262 miles (422 km) along Florida's west coast from an interchange with US 41 in Memphis, south of Tampa, and continues to the Georgia border north of Monticello.

According to a Dateline NBC study, part of US 19 in Florida is the most dangerous road in the U.S. A Florida Highway Patrol test period beginning in 1998 and ending in 2003, as mandated by the National Highway Traffic Safety Administration, showed the stretch of US 19 from Pasco to Pinellas county to average approximately 52 deaths a year, or 262 deaths in the five-year duration of the study.

Between the former and current terminus of CR 1, US 19 is dotted with independent motels, one of which was plagued with so much flooding during the early 21st Century that it was torn down.

Despite efforts to preserve some of the land in this section, a new gated community geared toward horse owners has sprung up north of Aripeka Road.

Tourist Development Council signs at both borders boast of the county being part of Florida's Nature Coast.

Osowaw and Tarpon boulevards were once part of the Old Dixie Highway, which crossed over US 19 and back until shopping centers and a portion of Timber Pines were built along the road.

The first is north of the Windward Village gated community, and the second is built around a local garage and former Sinclair gas station.

Berkley Manor Boulevard is the next intersection but strictly leads to another Deed Restricted Community in Spring Hill.

US 19 leaves Spring Hill north of Northcliffe Boulevard and enters Weeki Wachee, "the City of Live Mermaids".

Weeki Wachee Springs State Park, famous for the daily mermaid performances and the Buccaneer Bay waterpark is at the intersection of SR 50 (Cortez Boulevard).

Across the Hernando–Citrus county line, US 19 continues its rural surroundings, but this time has a limited number of left-turn lanes in the center median.

After the western terminus of Cardinal Lane, the road passes by Howard's Flea Market then curves to the northwest.

North of Homosassa Springs, US 19/US 98 serves as the location of a series of car dealerships, local garages, a Moose Lodge, churches, and the intersection of Ozello Trail (CR 494).

The division of this highway ends again, just south of the intersection of SR 44, where the road curves west as it approaches CR 495 (North Citrus Avenue).

Other former sections exist between Crystal River and Red Level, while the current US 19/US 98 passes by sparsely located hotels, bars, houses, cluster developments, and signs advertising locally-prepared peanuts.

A field where American Civil War reenactments are staged lies just north of the back entrance to a local quarry.

The Marjorie Harris Carr Cross Florida Greenway was the last section of US 19 that was two lanes wide in Citrus County.

A new four-lane divided bridge was completed by FDOT in the early-2010s,[9] which was originally planned in conjunction with the proposed Suncoast Parkway extension to Red Level.

North of Inglis, US 19/US 98 runs along sparse residences, trailer parks, a Florida Sheriff's Youth Facility, the Gulf Hammock Wildlife Management Area and eventually the Goethe State Forest.

Within the forest, the road crosses the Ten Mile Creek bridge before reaching an at-grade interchange with SR 121 and CR 336 in Lebanon Junction.

US 19/US 27 Alt./US 98 makes a sharp left turn near the intersection of SR 26 in Fanning Springs, where it also crosses the Joe H. Anderson Sr. Bridge over the Suwannee River, thus entering Dixie County.

It then follows the left bank of the Suwannee River and intersects the eastern terminus of CR 55A, and even contains a truck weight station in the median before reaching SR 349 in Old Town, which used to be US 129 Alt.

After the second crossing of CR 358, it begins to take an even more northerly direction before leaving Dixie County at the Steinhatchee River.

US 19 was extended to its southern terminus of Memphis in September 1954, when the original Sunshine Skyway Bridge opened to traffic.