Its eastern terminus is Palm Beach, Florida, at State Road A1A (SR A1A) near the Mar-a-Lago resort.

[citation needed] At Hattiesburg, an interchange with U.S. Route 49 provides four-laned access to Gulfport (to the south) and Jackson (to the north).

Passenger car traffic passes directly into town under the Mobile River via the Bankhead Tunnel.

The existing route between Semmes and the Mississippi state line is a two-lane undivided highway, and widening the route has been delayed due to a lack of budget and concern over pollution of Big Creek Lake, which supplies drinking water to the city of Mobile and other area towns.

Concurrencies include US 441 from Royal Palm Beach to Okeechobee, US 27 from South Sebring to West Frostproof, US 17 from Fort Meade to Bartow, US 301 from Clinton Heights to Moss Town, SR 50 from Ridge Manor to Brooksville, SR 50A then US 41 in Brooksville, US 19 from Chassahowitzka to Perry, ALT US 27 from Chiefland to Perry, US 319 in Medart and from St. Theresa to Port St. Joe, and US 90 in Pensacola.

There is a 60 mph speed limit east of Tyndall Air Force Base outside of Panama City all the way to Perry.

[4] [5] Blue Mountain recorded a song titled "Bloody 98," specifically referring to a two-laned section of the highway between Mobile, Alabama and Hattiesburg, Mississippi.