The major interstate highway that runs through the Southwestern United States is I-10.

Interstate 10 (I-10) is one of the longest east-west highways in the United States, stretching from Santa Monica, California, to Jacksonville, Florida. In the Southwest, I-10 passes through key cities such as Phoenix, Tucson, and El Paso, making it a vital transportation route. This interstate connects several states, including Arizona, New Mexico, and Texas, and traverses diverse landscapes, from arid deserts to bustling urban centers. I-10 is essential for trade, travel, and commerce in the region, and it plays a pivotal role in linking the Southwest to other parts of the country.