U.S. Route 35 (US 35) is a north-south United States highway that runs northwest-southeast for approximately 412 miles (663 km) from northern Indiana to the western suburbs of Charleston, West Virginia. The highway's northern terminus is in Michigan City, Indiana, at U.S. Route 20. Its southern terminus is in Scott Depot, West Virginia, at Interstate 64. Currently, the West Virginia portion of the highway is being expanded to four lanes, mostly along a completely new route. The Ohio portion has already been upgraded to a four-lane highway/freeway between the West Virginia state line and Trotwood, west of Dayton, Ohio.

In West Virginia from Scott Depot to Point Pleasant, US 35 is currently being expanded to a four-lane expressway. Currently the route is four lanes from I-64 to the junction with the bridge to Buffalo (West Virginia Route 869), which serves the large Toyota engine and transmission plant in Buffalo, and continues as a 2-lane route for 12 miles (19 km) to another four lane section of eight miles (6 km) to the Ohio River, which is the state line.

The remaining 12 mile gap is currently "unfunded". A possibility of completion as a toll road has been put forward.[citation needed]

Officially, US 35's new alignment begins at I-64 Exit #40 near Scott Depot, from which point US 35 proceeds north on its new roadway.

Signed east-west in Ohio, US 35 crosses the Ohio River on the Silver Memorial Bridge and enters Ohio. The first interchange is located adjacent to the Gallia-Meigs Regional Airport in Gallipolis as well as State Route 7. From there, it continues as a full freeway towards Jackson, with interchanges at SR 160, SR 850, and SR 325. Passing Rio Grande, the highway becomes a four-lane at-grade expressway when it reaches Centerville. This setup continues until SR 32 where the highway bypasses Jackson. A strange interchange configuration currently exists at US 35 and SR 32 - an interchange called a windmill interchange. Each highway has ramps that exit to the other highway ending at an intersection that one can travel either direction. This is odd because both highways end up having at-grade intersections, albeit with a grade-separation of the main highway corridors. Continuing west, the highway reverts to an expressway until it reaches Richmond Dale. The section between Richmond Dale and Chillicothe was upgraded to a full freeway in 2005 and includes a large cut through a 1,000 feet (300 m) ridge. This section of road provides westbound motorists with a panoramic view of the Scioto River valley. Travelers eastbound at Chillicothe near the Bridge Street exit can see the hills that are shown on the Great Seal of the State of Ohio. The next major interchange is with Interstate 71 in Jeffersonville. As the route continues through flat farmlands, it has a full-access interchange with I-675 in Beavercreek. Several miles later, US 35 opens into a three-lane highway (with five lanes in some parts) through downtown Dayton and has another full-access interchange with Interstate 75 in downtown Dayton. The Ohio portion of US 35 merges with Interstate 70 near New Paris. The portion of US 35 from the western edge of Dayton to the merge with I-70 is the only two-lane section remaining, passing through the city of Eaton. US 35 is a major Appalachian corridor linking I-70 and points west to I-64 and points east.

The portion of the route between Jackson and Gallipolis is known as the Bob Evans Highway. This section is designated as a Welsh Byway by the Ohio Department of Transportation as well.

US 35 enters Indiana with I-70, and splits off on the northwest side of Richmond. US 35 then travels in a northwest path through the cities of Muncie, Kokomo, Logansport, Winamac, Knox and La Porte before terminating at US 20 in Michigan City.

As of June 15, 2009, the old segment of US 35 between Buffalo Bridge, West Virginia and US 60 is now signed as West Virginia Route 817.

On October 1, 2009, the State of Indiana transferred the western 5.31 miles (8.55 km) of US 35 to Michigan City's local highway system. US 35 in Michigan City is currently being served by commercial traffic that travels in and out of downtown (where it originally terminated at US 12); according to local traffic counts, only half of the measured traffic on US 35 is through traffic. After the transfer of control, Michigan City began reconstructing the road using local, state and federal-aid funds. The change was approved by AASHTO on October 17, 2008.

List of unused highways in Ohio