In the U.S. state of Indiana, Interstate 70 travels east–west across the state passing through Indianapolis. Interstate 70 crosses into Indiana near Terre Haute and crosses into Ohio in Richmond. It covers 156.60 miles in Indiana. It parallels U.S. Route 40, the old National Road.

The Indiana portion of Interstate 70 begins on the Illinois border west of Indianapolis, near Terre Haute. Heading east, I-70 crosses the Wabash River soon after crossing into Indiana. US 40 runs concurrent with I-70 briefly before breaking off and travelling north of I-70. The interstate then crosses through Terre Haute. I-70 intersects with US 41 and US 150 in Terre Haute. Just outside the city, I-70 passes near Terre Haute International Airport. I-70 continues to the northeast towards Indianapolis.

Interstate 70 passes near the Indianapolis International Airport before intersecting with I-465. The interstate crosses the White River before passing south of downtown Indianapolis. The section of I-70 along the east side of downtown Indianapolis overlaps Interstate 65. The junctions are often referred to as the "North Split" and the "South Split," forming the eastern leg of a section of freeways and surface streets locally known as the "Inner Loop" (as opposed to the "Outer Loop" of the I-465 beltway). The north split is also called the "Spaghetti Bowl" due to the visual complexity of the overlapping freeways, ghost ramps and overpasses that were originally intended as a connection to a never-built portion of Interstate 69. East of the downtown area, I-70 intersects with the I-465 loop and traverses east towards Ohio. I-70 reaches a maximum width of five lanes in the Indianapolis area.

A portion of I-70 east of Indianapolis is known as the "Anton Tony Hulman Jr. Memorial Way." Tony Hulman is most known for rescuing the Indianapolis Motor Speedway in 1945 and making the Indianapolis 500 popular. I-70 does not intersect any significant cities until it reaches Richmond. It does pass within proximity of Greenfield and New Castle. On the northwest side of Richmond, US 35 joins I-70 until it crosses into Ohio. It also intersects with US 27 providing access to Richmond south of the interstate. On the east side of Richmond, US 40 intersects with I-70 immediately to the west of the Ohio border.