It runs from Crystal River on the Gulf of Mexico east to New Smyrna Beach on the Atlantic Ocean, passing through Inverness, Wildwood, Leesburg and DeLand.

A section in Lake County, between eastern Leesburg and a point north of Mount Dora, is concurrent with U.S. Highway 441 (SR 500).

SR 44 runs directly east, until it leaves the city limits, then makes a sharper southeastern turn prior to the intersection of North Dunkenfield Avenue and West Norvell Bryant Highway (County Road 486).

It briefly turns east again as it reaches the intersection of Rock Crusher Road, but curves back to the southeast roughly a mile later.

Near a pair of shopping centers, the divider ends east of Croft Avenue, and the road resumes its status as an undivided four-lane highway with center-left turn lanes.

East of US 41, SR 44 runs over the Withlacoochee State Trail with bike ramps on both sides, and then along the southern shore of Lake Henderson.

The rest of the road is surrounded by farms, parkland, and boat launching areas, especially as it gets ready to cross the Withlacoochee River at the Citrus-Sumter County Line, where it enters Rutland.

As the road enters Wildwood it is lined with truck stops, travel plazas, hotels, and other tourist attractions surrounding the interchange with Interstate 75 as well as Florida's Turnpike.

After straightening out again, it approaches a four-lane bridge over the CSX Wildwood Subdivision that was completed in 2010, just before the road intersects with US 301.

East of US 301, the road takes another slight southeastern curve where it passes through the recently expanded community of The Villages, Florida and later meets the eastern terminus of County Road 44A and then CR 468 in the former community of Orange Home, just before crossing the Lake County Line.

A former railroad line running from Wildwood to Leesburg that ran along the south side of CR 44A runs along the north side of the road, when CR 44A ends Before reaching Downtown Leesburg, SR 44 makes a sharp right turn onto a truck bypass at the intersection of Main Street and County Road 468.

The road curves to the northeast again at Lake Port Boulevard and crosses the same abandoned railroad line that originated in Wildwood.

From there the road turns right onto East Orange Avenue, which continues Route 44's status as a two lane rural scenic highway.

The road begins to move southeast from Talmadge Gardens Road to East Voorhis Avenue then takes a south turn along the west coast of Lake Winnemisett and becomes a four-lane divided highway again at the south end of Lake Winnemisett.

It then bypasses a former section of SR 44 just before it approaches Interstate 4, which contains partial cloverleaf ramps on the southwest and northeast corners of the bridge.

From the 1945 Great Renumbering, until the mid-1960's, the segment between US 17/92 in DeLand and US 1 in New Smyrna Beach was part of Florida State Road 40.

[4] The segment even included a Florida State Road 40A along Pioneer Trail, which remained in place even after the realignment of SR 40 from Barberville to Ormond Beach.

The suffix, "W", was most likely added to not confuse this section with State Road 44, to the north, and to show its location by being west of US 19 and US 98(SR 55).

County Road 44A then not only crosses US 301 to enter Huey Street, but the wye for the former Leesburg and Tavares railroad line.

One block away, CR 44A breaks away from Huey Street and curves south before running along the north side of the right-of-way of the previously mentioned abandoned railroad line.

[10] It then passes by Lake Joanna before terminating at State Road 44 between the towns of Eustis and Mount Dora.