Is there a train to Indianapolis?

Amtrak's Cardinal line stops in Indianapolis, but there is no rail service from Cape Girardeau.

How long is the drive?

The drive takes about 5 hours and 30 minutes.

Yes, some sections of the Indiana road network may have tolls.

What is the best route?

I-64 East to I-65 North is the standard and most efficient route.

There are no direct commercial flights between these two cities.

Cape Girardeau

Indianapolis

Driving

Cape Girardeau to Indianapolis

Updated: 28 May 2026

The journey from Cape Girardeau to Indianapolis covers approximately 350 miles. You will head east on IL-146 and I-64 through southern Illinois, then transition to I-65 North in Louisville to reach Indianapolis. This route takes you through the scenic Shawnee National Forest area and across the Ohio River. The total driving time is approximately 5.5 hours. It is a popular route for those traveling from the Mississippi River valley into the Midwest.

Total Distance: 563 km driving distance, 460 km straight-line air distance.

Fastest Way

Driving via I-64 and I-65 is the fastest and most direct route.

Cheapest Way

Driving your own vehicle is the most cost-effective way to make this trip.

Compare Cape Girardeau to Indianapolis Routes

Driving

Direct

Duration

5 hours 30 mins

Avg Price

$60-$80 in fuel

Operator

Personal Vehicle

Route

IL-146 East to I-64 East, then I-65 North to Indianapolis.

Be prepared for tolls on certain sections of the Indiana road network.

Travel Tips

Louisville Traffic
Expect heavy traffic when passing through Louisville on I-65.
Rest Stops
There are plenty of service plazas along I-65 in Indiana.
Dining
Stop in Louisville for a wide variety of dining options before the final leg to Indianapolis.
Navigation
Use a GPS to navigate the complex highway interchanges in Indianapolis.
Fuel
Gas prices are often lower in rural Illinois than in the major cities.

Safety Tips

Construction
Watch for road work zones on I-65, which are common in Indiana.
Weather
Be prepared for snow or ice in the winter months.
Road Hazards
Stay alert for wildlife in the rural sections of southern Illinois.
Visibility
Use your headlights during heavy rain or fog.