U.S. Route 98 is an east–west United States highway that runs from western Mississippi to southern Florida. It was established in 1933 as a route between Pensacola, Florida and Apalachicola, Florida, and has since been extended westward into Mississippi and eastward across the Florida Peninsula. It runs along much of the Gulf Coast between Mobile, Alabama and Crystal River, Florida, including extensive sections closely following the coast between Mobile and St. Marks, Florida.

As of 2005, the highway's western terminus is near Washington, Mississippi, at U.S. Route 61. Its eastern terminus is Palm Beach, Florida, at State Road A1A.

U.S. 98's western terminus is in Mississippi, and its eastern terminus is in Florida. Much of its route through Alabama and Florida falls within coastal counties.

Within Florida, US 98 is marked as an east–west road from the Alabama-Florida border to Perry. Throughout most of the state, the road is marked as a north–south road.

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. The hidden designation for most of US 98 across the panhandle of the state of Florida is State Route 30. Between Chassahowitzka and Palm Beach, the hidden designation is State Route 700. There is a 60 mph speed limit east of Tyndall Air Force Base outside of Panama City all the way to Perry.

In Alabama, U.S. 98 is paired with unsigned Alabama State Route 42. The route enters Alabama from the east near Lillian in rural Baldwin County. At Daphne, U.S. 98 begins a concurrency with U.S. Route 90. U.S. 90 and 98 junction Interstate 10 at Daphne on the eastern shore of Mobile Bay, then again on the western side of the bay as they enter downtown Mobile. As the two routes approach the Mobile River, U.S. 98 is split into two routes, with a Truck Route 98 crossing the Mobile River via the Cochrane–Africatown USA Bridge, co-signed with U.S. 90. Passenger car traffic passes directly into town under the Mobile River via the Bankhead Tunnel. Once the Truck Route rejoins the main route in downtown Mobile, U.S. 98 assumes a northwestward trajectory, and enters Mississippi near the community of Wilmer in western Mobile County. U.S. 98 is the southern terminus of two major U.S. highways: U.S. Route 31, at Spanish Fort, and U.S. Route 45 in Mobile.

U.S. 98 enters the state from the southeast and immediately widens to four lanes. It bypasses Lucedale to the north, and an interchange with Mississippi Highway 63 provides four-laned access to Pascagoula on the Mississippi Gulf Coast, increasing road capacity for hurricane evacuations.[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). The road continues west from its intersection with U.S. 49 to Interstate 59 at Exit 59, with which it is concurrent through Exit 65 (Hardy Street). The highway runs westward through Columbia before meeting U.S. 51 in McComb. It then joins Interstate 55 from Exit 15 (South McComb) to Exit 20 (Summit). The last remaining two-laned section of U.S. 98 in Mississippi then runs northwestward to Bude and Meadville, becoming concurrent with the four-laned US 84 from Meadville to its western terminus in Washington at U.S. 61, just northeast of Natchez. There is some debate as to whether the highway actually runs with U.S. 61 to Natchez.[citation needed]

U.S. 98 serves as a primary hurricane evacuation route in southern Mississippi, connecting cities along the Mississippi Sound to inland destinations further north.

The Mississippi section of U.S. 98 is defined in Mississippi Code Annotated § 65-3-3.

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