The northern section of US 285, from Santa Fe to Denver, traverses mountainous and rocky terrain; with that in mind, anyone using the road should check weather conditions during the winter months.

The route then traverses the Carson National Forest where 285 now makes a long climb up to the Colorado Plateau, passing through Ojo Caliente as it ascends to the San Luis Valley.

After crossing US 64, the highway passes through the village of Tres Piedras, New Mexico at the south end of the valley, then proceeds north to the Colorado border.

On March 7, 2019, the Legislature of the State of New Mexico, in a unanimous vote, named the 27 mile section between Clines Corners and Encino the "Representative Lorenzo "Larry" Larrañaga Corridor".

[2] Heading north from the Colorado border, US 285 passes through the main part of the San Luis Valley, eventually reaching Alamosa.

The highway brushes Salida and follows the Arkansas River north up the valley, then takes a sharp eastward turn just before the small town of Buena Vista.

On March 14, 2008, both houses of the Colorado legislature, in a unanimous vote, named the section between Kenosha Pass and C-470 the Ralph Carr Memorial Highway.

[3][4] The short segment between US 50 at Salida and US 24 at Buena Vista closely parallels the original U.S. Route 650,[5] which was designated in 1926, but eliminated in 1936 when US 285 was commissioned along its present extent from Sanderson to Denver, mostly replacing state-numbered highways.