In the initial assignment of state highways in 1917, Dallas-Fort Worth and Houston were connected by a branch of State Highway 2, which ran via Waco and Bryan and continued on to Galveston. The more direct route followed by US 75 was not initially part of the system between Richland and Huntsville. This Richland–Huntsville cutoff was added by 1919 as SH 32, and US 75 was assigned to the alignment, as well as SH 6 north of Dallas, in 1926. The branch of SH 2, which US 75 followed between Houston and Galveston, eventually became part of SH 6, and these numbers were dropped in the 1939 renumbering. 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. However, the highways in and near these cities included some of the first freeways in the state: the Gulf Freeway and the Central Expressway. When Interstate 45 was built in the 1960s, its alignment bypassed many of the towns and built-up areas between downtown Dallas and Houston. The bypassed routes retained the US 75 designation until the designation was truncated to downtown Dallas in 1987. Many of the original alignments continue to exist under other designations. In Dallas, the route followed what is now the Good Latimer Expressway southeast, out of downtown, along US 175 and south along State Highway 310. Near Ferris, Trumbull, Palmer, Ennis, and Corsicana Interstate 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:
US 75 enters Texas from Oklahoma just north of Denison, crossing the Red River. At this point it is concurrent with US 69, but the two separate about south of the river. US 75 continues to the south and southwest to loop around the western side of Denison. The route continues south reaching Sherman and a limited-access, three-level intersection with US 82. US 75 then continues southward to cross US 380 on the north side of McKinney. The stretch through McKinney is largely unchanged from its original design except for its intersection at the Sam Rayburn Tollway. to replace the original interchange. Plans to upgrade the facility through and north of McKinney are under way with the reconstruction of the US 380 bridge. The highway continues southward into the northern suburbs of Dallas where it intersects the President George Bush Turnpike and I-635. The route reaches its southern terminus on the east side of downtown Dallas, intersecting Spur 366 and ending at unsigned I-345. The exit numbers for US 75 are not based on mile markers; instead, the exits were numbered consecutively. As the bypass route was completed around the Sherman–Denison area, the numbering system was continued for the new exits. Upon completion of the widened Central Expressway through Dallas, the exit numbering was changed for the section south of I-635 to correspond with the new exits, based on mileage, but the numbering system north of I-635 was left unchanged, thus explaining the gap in the current numbering system.