It heads south in a concurrency with U.S. Route 77, then turns east on North Avenue.

Business US 60 in Ponca City begins at an interchange with US 60 and US 177 (the E. W. Marland Memorial Highway) and continues east down South Avenue.

The road briefly forms a concurrency with Business I-49, before turning off and heading north on Neosho Boulevard.

After leaving Verona, the road heads east through a rural area becoming South Street in Aurora.

It rejoins the main route east of Mountain Grove at the unincorporated community of Dunn.

West of the city, the business route leaves the main highway at an interchange and enters Cabool as Ozark Street.

Ozark Street curves to the northeast, eventually intersecting U.S. Route 63. Business 60 turns south in a concurrency with US 63 and rejoins the main highway southeast of Cabool.

In downtown Willow Springs, Business 60/63 intersects Route 137 at Harris Street.

Business US 60 in Van Buren begins in the southern part of the city, leaving the main highway going west on James Street.

Business US 60 in Poplar Bluff begins in the northwest corner of the city at the interchange of US 60 and US 67 (Future I-57).

Business US 60 in Sikeston begins southwest of the city, turning north off the main highway at a junction with Route FF.

The road turns east at the terminus of Route 114 and becomes Malone Avenue, paralleling the Union Pacific Railroad tracks.

The highway curves around, rejoining the main route in the southwest part of Cloverport.

Alternate US 60 in Louisville begins at the intersection of the Dixie Highway (US 60 and U.S. Route 31W) and KY 2049, turning east onto 7th Street Road.

It zigzags through the area, following Berry Boulevard, Taylor Boulevard, Central Avenue (at the entrance to Churchill Downs racetrack, home of The Kentucky Derby and Kentucky Oaks), Crittenden Drive, and Eastern Parkway.

It rejoined the bypass route on the east side of Lexington at New Circle Road.

After leaving Clifton Forge, Business US 60 joins non-special U.S. Route 220 and passes through Cliftondale Park before rejoining the main highway at the I-64 exit 27.

Truck US 60 in Richmond begins where US 60 turns north from Midlothan Turnpike onto Roanoke Street.

It was united with U.S. Route 70 from Globe to Peridot, then turned north through Fort Apache, Whiteriver, McNary, and Eagar, Arizona.

Bypass US 60 was a loop around the city of Owensboro; the main route passed through the downtown area.

In April 2011, in conjunction with the KY Transportation Cabinet, U.S. 60 no longer passes through downtown and the former "bypass" is the main U.S. 60 route.