U.S. Route 31 (US 31) is a part of the United States Numbered Highway System that runs from Spanish Fort, Alabama, to the Mackinaw City, Michigan. In the U.S. state of Indiana, it is a State Road that enters the state via the George Rogers Clark Memorial Bridge between Louisville, Kentucky, and Clarksville, Indiana. The 266.02 miles (428.12 km) of US 31 that lie within Indiana serve as a major conduit. Some of the highway is listed on the National Highway System. Various sections are rural two-lane highway and urbanized four-lane divided expressway. The northernmost community along the highway is South Bend near the Michigan state line.

US 31 was first designated as a US Highway in 1926. A section of the highway originally served as part of the Dixie Highway. US 31 replaced the original State Road 1 (SR 1) designation of the highway which dated back to the formation of the Indiana State Road system. SR 1 ran from Clarksville through Indianapolis to South Bend and ended at the Michigan state line. Realignments and construction projects have expanded the highway to four lanes north of Columbus.

Only the segment of US 31 that is north of Indianapolis is included as a part of the National Highway System (NHS). The NHS is a network of highways that are identified as being most important for the economy, mobility and defense of the nation. The highway is maintained by the Indiana Department of Transportation (INDOT) like all other U.S. Routes in the state. The department tracks the traffic volumes along all state highways as a part of its maintenance responsibilities using a metric called average annual daily traffic (AADT). This measurement is a calculation of the traffic level along a segment of roadway for any average day of the year. In 2010, INDOT figured that lowest traffic levels were the 3,690 vehicles and 160 commercial vehicles used the highway daily near Memphis. The peak traffic volumes were 168,770 vehicles and 18,090 commercial vehicles AADT along the section of US 31 concurrent with Interstate 465 (I–465).

US 31 overlaps I-65 in Jeffersonville, after crossing the George Rogers Clark Memorial Bridge from Kentucky. It then diverges as the access frontage lanes before splitting off north of Jeffersonville at Clarksville and proceeding to Indianapolis. The stretch of US 31 that runs through Columbus is the only inter-metropolitan stretch of the route that consists of a single lane in either direction. Construction has begun to widen US 31 to two lanes in both directions for its length through Columbus.

At I-465 on the south side of Indianapolis, US 31 is routed onto I-465 to the east of the city. This is the closest approach the highway makes to downtown Indianapolis. (Previously the route of the highway through Indianapolis was on East Street, Madison Avenue, North Street, and then Meridian Street.)

US 31 exits I-465 (coincidentally at Exit 31) in southern Hamilton County, and continues northward, primarily as a divided highway. US 31 then passes through or near Carmel, Kokomo, Rochester, Plymouth, and Lakeville. As US 31 approaches southern South Bend, the route becomes a full interstate-grade freeway as it converges with US 20/St. Joseph Valley Parkway and proceeds west then north, bypassing South Bend and proceeding into Michigan. (See U.S. Route 31 in Michigan.)

US 31 was signed by the Governor on March 7 of 1917, as Main Market Highway 1, signs were installed on June 1 of the that year. The name was changed to Indiana State Road 1, within a year, when Indiana began the state road system. By 1924, most of the route was paved, leaving only from Columbus to Franklin and from Peru to Plymouth that was unpaved. In 1926, US 31 signs were installed along what was SR 1 at the time. By 1927 the whole route through Indiana was paved.

Three sections of US 31 in Northern Indiana are being relocated or upgraded. All are part of the Indiana Department of Transportation Major Moves Project designed to convert US 31 to Interstate-grade freeway from South Bend to Indianapolis. The conversion of these over-capacity segments is expected to be completed in 2015. Funding has yet to be approved for the 78 miles of US 31 located between these three segments.

The New US 31 Plymouth to South Bend project will relocate US 31 on primarily new alignment from US 30 near Plymouth to US 20/St. Joseph Valley Parkway south of South Bend. Groundbreaking for the project occurred on September 17, 2008, and the first portions to be completed will be overpasses at two locations, Lilac Road and Plymouth-Goshen Trail in northern Marshall County. This section of highway is scheduled to open by the end of 2014.

The Kokomo Corridor Project will cover 14 miles (23 km) of new highway primarily in Howard County. The new limited-access highway will be east of Kokomo and will have four interchanges at SR 26, E. Boulevard (CR 100S), US 35/SR 22 (Markland Avenue), Touby Pike and US 35 north of Kokomo. Groundbreaking for the project occurred in the afternoon of September 17, 2008, only hours after the groundbreaking for the South Bend-to-Plymouth stretch. This section of highway is scheduled to be completed in 2013.

The New US 31 Hamilton County project will upgrade US 31 to freeway standards from near SR 38 north of Westfield to Interstate 465 near the Marion County line and Indianapolis. Construction is expected to be completed by 2015.