Interstate 25 begins at Interstate 10's exit 144 in Las Cruces. Immediately, three exits provide access to the city, including one for U.S. Route 70. After this, there are no major cities along the corridor until Albuquerque. However, when I-25 reaches Truth or Consequences, it is parallel to Elephant Butte Reservoir State Park.
As I-25 nears Albuquerque, it has interchanges with roads such as U.S. Route 380 and a concurrency with Route 60. Getting even closer, State Road 6, the original U.S. Route 66, meets up with I-25 in Los Lunas. Now getting even closer to Albuquerque, there are frequent exits to city streets, along with a huge interchange with Interstate 40. Named the Big I, it was given an honorable mention by the United States Department of Transportation and the Federal Highway Administration for excellence in urban highway design in 2002.
Leaving Albuquerque, I-25 starts to curve into an east¨Cwest orientation as it heads toward Santa Fe. I-25 retains that orientation until Las Vegas, where it starts to revert back into its usual north¨Csouth orientation. The highway stays this way as it leaves New Mexico and enters Colorado.
Interstate 25 has many nicknames though the state's larger cities. In Denver it is called the Valley Highway, the section in El Paso County is named the Ronald Reagan Highway, and through Pueblo it is named the John F Kennedy Highway.
I-25 enters Colorado 14 miles south of the city of Trinidad. It is the main north-south route through Colorado with a length of 300 miles. The Interstate exits Colorado in the north about 8 miles south of Cheyenne, WY. I-25 serves all the major cities in Colorado east of the Rocky Mountains, such as Denver, Colorado Springs, Pueblo and Fort Collins. Almost the entire way, from the north to the south, the Rocky Mountains are clearly visible.
There are also several military bases along the route, such as Cheyenne Mountain, Fort Carson and the Air Force Academy.
The section of I-25 between the northern border of Pueblo County, Colorado and the New Mexico state line is named the "John F. Kennedy Memorial Highway", in honor of President Kennedy's support of water resource development in the Arkansas Valley.
I-25 enters Wyoming 8 miles south of the state capital, Cheyenne. After traveling through downtown, the interstate continues north to Douglas, Wyoming, passing many plateaus and train tracks. Commonly, very long trains can be seen slowing moving beside the interstate. Around Douglas, the interstate curves to the west towards Casper. Once in downtown Casper, I-25 sharply turns north and continues to Buffalo, where it merges with I-90 and ends.