I-64 crosses the Wabash River and enters the state of Indiana. It passes Indiana 69 and Indiana 165, and also passes under Indiana 68 (no direct interchange serves Indiana 68, though one can access said route from either Indiana 165 or 65) then passes three officially marked exits for Evansville (Indiana 65, US 41, and Interstate 164/Indiana 57/Future Interstate 69) then proceeds to service exits leading to Jasper, Santa Claus and Indiana 37, and intersects Interstate 265 in New Albany before crossing into Kentucky on the Sherman Minton Bridge.

The section of Interstate 65 in downtown Indianapolis multiplexes with Interstate 70. The junctions are often referred to as the "North Split" and the "South Split", forming a section of interstate locally known as the "Inner Loop" or "Spaghetti Bowl" due to the visual complexity of the multiplexing freeways.

An interstate highway in the Southern and Midwestern United States. It currently exists in two discontinuous sections: one from Indianapolis, Indiana, at Interstate 465 to the U.S. side of the Blue Water Bridge in Port Huron, Michigan, at the Canadian border, where it continues as Highway 402 in Ontario, and one section connecting U.S. 61 and Interstate 55 in northwestern Mississippi.

Terre Haute. The only major city is Indianapolis. Interstate 65 can be accessed from downtown, while the other Interstates in the city, Interstate 74 and 69, must be accessed from Interstate 465, the beltway around the city. After passing through, it continues east through eastern Indiana before exiting into Ohio in Richmond, with U.S. Route 35.

Interstate 74 runs east from the Illinois state line to the Crawfordsville area before turning southeast. It then runs around the city center of Indianapolis along Interstate 465. It then enters Ohio near the metropolis of Cincinnati, Ohio.

In the state of Indiana, Interstate 90 enters from Illinois at the Chicago Skyway. It then runs to the concurrency of Interstates 80/94 east of Interstate 65, where I-80 leaves I-94 and joins with I-90. The combined I-80/90 route runs east across northern Indiana and near the southern border of Michigan to the Ohio state line.

in the U.S. State of Indiana is a route that travels the south central part of the state from west to east. The western terminus is near Hazleton at U.S. Highway 41. The eastern terminus is at U.S. Highway 50 in Aurora, along the Ohio River southwest of Cincinnati.

at one time ran from the northeast of the state to the south end. In the pre-Interstate Highway era, Indiana 37 was the most direct route between Fort Wayne and Indianapolis, although Interstate 69 has supplanted it and some other highways as through routes. It remains as the principal link between Indianapolis and Bloomington.

In the state of Indiana, U.S. 150 runs south with U.S. Route 41 from Terre Haute. It is then multiplexed with its parent, U.S. Route 50 from Vincennes to Shoals. It then runs east to New Albany before multiplexing with Interstate 64 into Kentucky.

U.S. Route 24 runs east from the Illinois state line to Huntington. At Huntington, US 24 turns northeast and runs to Fort Wayne it then multiplexes with Interstate 69 and Interstate 469 to bypass the city before entering Ohio at the state line northeast of Fort Wayne. The segment of US 24 between Logansport and Toledo, Ohio is part of the Hoosier Heartland Industrial Corridor project of the Intermodal Surface Transportation Efficiency Act.

U.S. Route 31 is a long north-south highway connecting northern Michigan to southern Alabama, with termini at Interstate 75 near Mackinaw City, Michigan, and U.S. Route 90 and U.S. Route 98 at Spanish Fort, Alabama. It formerly reached Mackinaw City along the southern approaches of the Mackinac Bridge (Interstate 75) in the north and downtown Mobile, Alabama, in the south.

Enters Indiana at the Wabash River, bypassing Vincennes and Washington and passing through Bedford, Seymour, and Versailles. It meets the Ohio River at Aurora, and soon crosses into Ohio, running through downtown Cincinnati via Fort Washington Way.

U.S. 6 crosses the state line and shares the same Borman Expressway with Interstate 80/94 through Hammond and Gary until State Road 51 Exit 15; it goes south for about 2 miles and turns east until it meets U.S. Route 421 in Westville, then goes south for a mile then east until it meets U.S. Route 35 and U.S. Route 31, and it shares the same road with U.S. Route 33 for about 5 miles until U.S. Route 33 breaks south toward Fort Wayne, IN at Ligonier, IN, and then it is mostly two lanes through Indiana until it meets the Ohio state line just east of Butler, Indiana. Before the Borman Expressway was completed, U.S. 6 was on Ridge Road, portions of which are now signed Business U.S. 6.