I-45 replaced U.S. 75 over its entire length, although portions of U.S. 75 remained parallel to I-45 until its elimination south of downtown Dallas in 1987. At the south end of I-45, State Highway 87 (formerly part of U.S. 75) continues into downtown Galveston. The north end is at Interstate 30 in downtown Dallas, where U.S. 75 used the Good-Latimer Expressway. A short continuation, known by traffic reporters as the "I-45 overhead",[2] signed as part of US 75, and officially Interstate 345, continues north to the merge with former U.S. 75. Traffic can use Spur 366 to connect to Interstate 35E at the north end of I-345.

The portion of I-45 between Galveston and downtown Houston is known as the Gulf Freeway. The short Pierce Elevated connects this to the North Freeway, which leads to Conroe. I-45 and I-345 in the Dallas area, north of the interchanges with Interstate 20 and State Highway 310 (old U.S. 75), is the Julius Schepps Freeway. The Gulf Freeway and North Freeway both include reversible High-occupancy vehicle lanes for buses and other high-occupancy vehicles to and from downtown Houston.

I-45 map