The section of the Interstate system's route that passes through Oklahoma City was altered several times after it was established in order to accommodate the presence of the new freeways.

US-62 enters Oklahoma in Harmon County, 5 miles (8.0 km) west of Hollis.

[2] It then passes through that town, the county seat, where it serves as the southern terminus of State Highway 30.

The highway passes through unincorporated McQueen 4 miles (6.4 km)[2] and then enters Jackson County.

[2] US-62 continues eastward, sending US-62 BUS north to Snyder, which was the original US-62 alignment in the area.

US-62 serves as the southern terminus of the northern State Highway 54 3 miles (4.8 km) east of this.

[3] The road then enters Comanche County, where it serves as the southern border of Fort Sill.

Continuing east, US-62 becomes an expressway, Rogers Lane, that serves the north side of Lawton (along with several Ft. Sill gates).

In eastern Lawton, the highway has an interchange with Interstate 44 and begins a concurrency with it (joining at Exit 40B), along with US-277 and US-281.

The three U.S. routes split off at Exit 46, with I-44 continuing onto the northern section of the H. E. Bailey Turnpike.

The three routes continue into Anadarko, where State Highway 8 briefly joins the concurrency.

In eastern Harrah, the route meets the west terminus of State Highway 270.

[2] US-62 enters eastern Oklahoma's Green Country as it crosses into Okfuskee County west of Paden.

It begins to turn southeast, intersecting State Highway 48 west of Castle, before joining once again with I-40 near Okemah, at Exit 221.

The two U.S. routes split off at Exit 240B, where they continue the mainline of the Indian Nation Turnpike, which terminates at I-40.

The two U.S. routes serve eastern Henryetta, and west of Dewar, they are the western terminus of U.S. Highway 266.

Near Ft. Gibson, US-62 begins to concur with State Highway 10, and the two routes stay joined through Tahlequah.

The only portions of the highway that were paved were from Chickasha to Tabler, from Newcastle to Oklahoma City and Meeker, from Okemah to Morris, and from just south of the US-64 junction to Fort Gibson.

This routing was only meant to be temporary, following Agnew, Exchange, and Reno Avenues to downtown.

[7] This change was followed up by the September 4, 1963[7] rerouting, which put US-62 onto its present-day routing (though I-240 did not exist yet, and I-44 still ended at I-35).