The highway runs across the northeastern rural part of the state, connecting several population centers.

To the southeast of the city near the town of Sherman in Pontotoc County, I-22/US 78 has a second brief concurrency with MS 9 starting between the exits 73 and 76.

The freeway then turns eastward and has an interchange with MS 371 north of Mooreville before crossing into Itawamba County.

I-22/US 78 then turns east-southeastward with one final interchange (exit 113) with MS 23 south of Tremont before crossing into Alabama.

AASHO agreed to Hinkle's ideas, passing a resolution on November 20, 1924, to develop a better organized interstate highway system.

[3] With the exception of a break at the Tennessee-Tombigbee Waterway in Fulton, MS 178 is a complete route from Memphis, Tennessee, to the Alabama state line.