[4] These projects, and others in New Mexico, were necessary because these stretches of I-25 were originally inadequately designed and constructed (the pavement was deteriorating rapidly) and also because urban areas, like Albuquerque, Colorado Springs, and Denver, had tripled and quadrupled in population much earlier than anyone had anticipated back in the 1950s and 1960s.

I-25 begins at I-10's exit 144 in Las Cruces, just south of the New Mexico State University campus.

[6] When I-25 reaches Truth or Consequences, it is parallel to Elephant Butte Lake State Park.

[7] From Las Cruces to Santa Fe, I-25 follows the route of the Camino Real de Tierra Adentro.

[10] Through Albuquerque, I-25 is named the Pan American Freeway, and there are frequent exits to city streets.

[17] The highway maintains a north and northeast orientation as it leaves New Mexico traversing Raton Pass (7,798 ft or 2,377 m[18]) and enters Colorado.

[20] The designation of this highway, while clear in intent, has not seen widespread adoption in terms of signage or recognition, likely due to the irregular nature of the route.

I-25 crosses the Palmer Divide between Denver and Colorado Springs, providing some of the highway's most scenic views of the Rocky Mountains and its foothills.

Blizzards and high winds on this stretch (particularly over Monument Hill) are notorious for causing traffic problems during the winter months.

The section of I-25 that is between the northern border of Pueblo County and the New Mexico state line is named the "John F. Kennedy Memorial Highway" in honor of President Kennedy's support of water resources development in the Arkansas River Valley.

The section in New Mexico between Romeroville and Los Lunas closely follows the original alignment of US 66, which was later shortened and realigned to run due west from Santa Rosa.