[1] US 75 was previously a cross-country route, from Canada to the Gulf of Mexico at Galveston, Texas, but the entire segment south of Dallas has been decommissioned in favor of I-45; a cutoff section of town-to-town surface road having become Texas State Highway 75.

The stretch of US 75 between I-30 and the Oklahoma state line has exits numbered consecutively from 1 to 75 (with occasional A and B designations), excluding 9-19.

While US 69 continues to the northeast as a multilane highway, US 75 turns north to serve several small communities between Atoka and Henryetta.

Through travellers bypass this segment of US 75 via US 69 and the Indian Nation Turnpike, where the speed limit is 75 miles per hour (121 km/h).

From Henryetta through Tulsa and on through Bartlesville to the Kansas State Line, US 75 is once again a multilane highway.

From I-35 to Melvern Lake, US 75 is a Super-2 highway, with controlled access interchanges at Township Road, K-278, and K-31 southbound.

US 75 and US 20 run together on a freeway bypass around the southeast side of Sioux City before US 20 turns east at Gordon Drive.

US 75 enters Minnesota south of Luverne near Ash Creek and Steen, and passes through Pipestone, Canby, and Breckenridge.

US 75 does not cross the Red River, ending instead at the Canadian border at the unincorporated community of Noyes.

[3] Border traffic is instead directed to the nearby crossing in Pembina, North Dakota, (via MN 171, ND 59 and I-29).

All 408 miles (657 km) of US 75 in Minnesota is officially designated the Historic King of Trails, sponsored by the towns along the route.

[6][7] This Richland–Huntsville cutoff was added by 1919 as State Highway 32,[8] and US 75 was assigned to the alignment, as well as SH 6 north of Dallas, in 1926.

Prior to the coming of the Interstate Highway System in the late 1950s, the only improvements to US 75 in Texas beyond building a two-lane paved roadway were in the Houston and Dallas areas.

When Interstate 45 was built in the 1960s, its alignment bypassed many of the towns and built-up areas between downtown Dallas and Houston.

In Dallas, the route followed what is now the Good Latimer Expressway (formerly Spur 559)[10] southeast, out of downtown, along US 175 and south along SH 310.

[11] Near Ferris, Trumbull, Palmer, Ennis, and Corsicana I-45 veers east to avoid the more populated areas.

The old US 75 alignments through these towns, decommissioned in 1987, now carry the following designations: Through Streetman, Fairfield, Buffalo, Centerville, Madisonville, Huntsville, New Waverly, Willis, and Conroe, US 75 followed what is now SH 75.

"[23] Further, the City of Omaha refused to complete upgrades to the freeway, eliminating the possibility of achieving the I-580 designation planned for it.