James A. Rhodes Appalachian Highway, I 71 $south
357.4 mi6 hours 7 mins
| Head northwest on 5th Street (WV 14) | 0.3 mi | |
| Continue slightly right onto Parkersburg–Belpre Bridge | 0.5 mi | |
| Make a slight right | 100 feet | |
| Go straight onto Main Street (SR 32) | 0.8 mi | |
| Turn left onto James A. Rhodes Appalachian Highway (SR 32) | 15.1 mi | |
| Take the ramp onto US 50 | 21.3 mi | |
| Keep left onto Appalachian Hwy (US 50 W) | 0.3 mi | |
| Continue onto James A. Rhodes Appalachian Highway (US 50 W) | 0.5 mi | |
| Continue onto East Bentbrook Drive (US 50) | 7.1 mi | |
| Continue onto James A. Rhodes Appalachian Highway (US 50) | 128.3 mi | |
| Take the ramp towards I 275 South: Kentucky | 0.4 mi | |
| Merge left onto Cincinnati By-Pass (I 275 S) | 9.7 mi | |
| Continue onto Combs–Hehl Bridge (I 275 W) | 10.3 mi | |
| Take exit 84 towards I 71: Lexington | 0.3 mi | |
| Keep left towards I 71 South: Lexington | 1.4 mi | |
| Keep left at the fork | 0.7 mi | |
| Merge left onto I 71 S | 10.3 mi | |
| Take the ramp towards I 71 South: Louisville | 76.8 mi | |
| Take the ramp towards I 64 West: Saint Louis | 0.5 mi | |
| Merge left onto I 64 W | 65.9 mi | |
| Take exit 63 towards SR 162: Ferdinand | 0.4 mi | |
| Turn left onto Main St (SR 162) | 6.6 mi | |
| You have arrived at your destination |
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Parkersburg, West Virginia - Santa Claus, Indiana