Skirting the Mexican Border and the Rio Grande near El Paso, Interstate 10 crosses the vast expanse of West Texas. The freeway has some at-grade crossings rather than full interchanges at some locations because of the remote character of the highway and the extremely low traffic volumes of the region. Interstate 10 finally sheds its rural desert characteristics as it passes through San Antonio and connects to Houston.
Interstate 10 becomes the freeway of the Deep South, connecting Houston with New Orleans, Biloxi, Mobile, and Pensacola. Several major sections of the highway are elevated, especially those in Louisiana around the bayous. Interstate 10 is surrounded by trees in the Deep South, quite unlike the wide-open spaces of the West. The Mississippi Welcome Center, a replica of a plantation, is much more welcoming than the utilitarian California Rest Area west of Blythe.
In Tallahassee, the original routing of Interstate 10 in Leon County took the freeway into downtown Tallahassee via Gaines Street, presumably as an elevated structure (dubbed the "Seminole Expressway" since it bordered Florida State University to the south). Opposition from the city and the university caused it to be rerouted. A developer in the northern part of the city donated land to build Interstate 10 near the Killearn development that was starting in the 1970s.