Full travel from Orlando to Titusville on the Old Cheney Highway, however, is not possible due to the demolition of a bridge over the Econlockhatchee River.

State Road 408, also known as the East-West Expressway or Toll Road 408, from its western starting point near Ocoee to its eastern terminus near the University of Central Florida near Bithlo, runs almost directly parallel to SR 50, with most exits on the 408 being within a mile to 2 miles away from SR 50.

The East-West Expressway was originally designed to, and still does, relieve traffic congestion on SR 50 during rush hour.

East of Nightwalker Road and July Avenue, SR 50 enters land owned by the Southwest Florida Water Management District, and the right-of-way for a set of power lines.

Immediately after the entrance to the aforementioned Boy Scout Camp, the road intersects Oak Hill Hospital on the opposite side.

East of those three major shopping centers is a Wal-Mart Supercenter and a Sam's Club Warehouse on the same side of the street.

While SR 50 climbs a hill and then descends, Twin Dolphin runs parallel to the eastbound lane as it climbs its own hill but then terminates at the same eastbound lane before SR 50 intersects CR 585(Barclay Avenue) and the entrance to Brookridge.

Entering the unincorporated community of Ridge Manor West, the road approaches some hotels, gas stations and restaurants serving motorist and tourists on Interstate 75.

The shorter Paul N. Steckle Lane exists on the north side and contains a Hernando County Firehouse, local residences, and one entrance to the Cypress Lake Preserve.

When US 98 turns southeast toward Trilby, Dade City, and West Palm Beach, SR 50 continues east and narrows down to two lanes.

After this, the road passes by a sand mine, and the right-of way for an abandoned segment of Ridge Manor Boulevard, before it crosses the CSX's Wildwood Subdivision (part of the S-Line), and then serves as the northern terminus of CR 575 which becomes a State Road once it enters Pasco County.

Both SR 50 and the railroad bed pass through the rural unincorporated communities of Linden and then Mabel, which serves as the northern terminus for the General James A.

The divider is widened further at a BP gas station in a former fork in the road when SR 50 becomes a pair of one-way streets in Downtown Groveland.

The road's time in Killarney is short-lived though as it enters Oakland where it curves briefly to the northeast to encounter Florida's Turnpike, and the recently rebuilt Exit 272.

Lake Barton stretches from the vicinity of this intersection to the southwest corner of State Road 436 (Semoran Boulevard), which has had an interchange since 2010.

Further east within Bithlo, SR 50 serves as the western terminus of State Road 520 at an interchange with no exit numbers.

East of this interchange the road turns direct east again and passes through Christmas, a rural community containing various Christmas shops, trailer parks and the Jungle Adventures Nature Animal Park which boasts of having "Swampy" the world's largest alligator.

After crossing the third bridge along the river, it enters Brevard County and the name changes from East Colonial Drive to Cheney Highway.

From here it runs along the southern border of the Saint Johns National Wildlife Refuge, which terminates at the interchange with Interstate 95 at Exit 215.

SR 50 officially enters Titusville after passing by the entrance to The Great Outdoors Golf and Recreational Vehicle Resort, west of the I-95 interchange.

Before the 1945 renumbering, the route that became SR 50 had the following numbers: SR 50 was defined in the 1945 renumbering as: Since then, the following changes have been made: State Road 50 is being widened from a two-lane undivided highway to a four-lane divided highway from U.S. 301 in Ridge Manor to east of Sumter County Road 478A near Tarrytown.

At Ponce de Leon Boulevard (US 98/SR 700), it becomes concurrent with US 98, until its eastern terminus with SR 50 and Jasmine Drive.

While both segments go up and down steep hills in the heart of the city, the Broad Street (eastbound) section runs over an old railroad bridge built in 1936.

Turning south along East Jefferson Street near Roger's Christmas House, SR 50A & US 98 go down an easier hill where it curves to the left before the intersection with Martin Luther King Jr. Boulevard (formerly Summit Street/CR 581A), then zips past the northern terminus of CR 581 (Emerson Road), finally reuniting with SR 50, which US 98 becomes concurrent with until breaking away in Ridge Manor more than 12 miles (19 km) east.

County Road 550 begins at Bayport Park heading east, then later curves to the northeast until it approaches a seafood restaurant on the southwest corner of an intersection with CR 495, only to turn back east again over the tidal swamps of the coast, which are owned by the Chassahowitzka National Wildlife Refuge.

Curving southeast, the road passes by a fishing encampment and another restaurant before intersecting with CR 597 north of Weeki Wachee Gardens.

The road finally curves to the east before approaching preserved land near Weeki Wachee Springs and terminates at the intersection of US 19 and SR 50.