U.S. Route 19 in Florida runs 264 miles (425 km) along Florida's west coast from an interchange with U.S. Route 41 in Memphis, Florida, south of Tampa, and continues to the Georgia border north of Monticello, Florida.
US 19 remains independent of I-75, even as the routes converge in the Tampa Bay Area. The route is co-signed with Interstate 275 over the Sunshine Skyway Bridge, a cable-stayed bridge over the mouth of Tampa Bay, US 98 between Chassahowitzka and Perry, Alternate US 27 between Chiefland and Perry, and US 27 between and Perry and Capps.
The road begins at an interchange with U.S. Route 41 in Manatee County, and remains independent until the interchange with Interstate 275 at Exit 5, where it overlaps I-275 across the Sunshine Skyway Bridge, the terminus of which is at Interstate 275 & State Road 682 at Exit 17.
According to a Dateline NBC study, part of US 19 in Florida is the most dangerous road in the United States. 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 County to Pinellas County to average approximately 52 deaths a year, or 262 deaths in the 5-year duration of the study. 100 of these deaths were pedestrian related making US 19 the #1 worst road to walk on in these two counties. Multiple efforts to improve US 19 have been suggested to the FDOT.
Within Downtown St. Petersburg, US 19 crosses Alternate US 19, which used to serve as the southern terminus of Alt US 19 until 2006. US 19 runs along 34th Street until just south of the interchange at State Road 694 at Gandy and Park Boulevards in Pinellas Park. This interchange was intended for the formerly proposed Gandy Freeway. In eastern Largo, State Road 688 shares an interchange with the northern terminus of State Road 693, a road that leads to St. Pete Beach and was once part of State Road A19A. Immediately after this, the next interchange is at State Road 686, the road to the St. Petersburg-Clearwater Airport. State Road 60 is the site of the world's first Single-point urban interchange. Drew Street is north of the interchange, and for years has been a source of major accidents. By 2006, the freeway gap was filled between SR 60 and Sunset Point Boulevard, however the service roads terminate at a creek between Drew Street and Coachman Road, creating a traffic situation similar to that of the Oakdale Merge on Long Island, New York.
As of 2017, US 19 is built to freeway standards from just south of 49th Street N to just north of Tampa Road. The freeway is built in the style of many Texas freeways, with service roads along the length of the route and Texas u-turns at major interchanges.