Heading from the Oklahoma border, US 287 and US 385, upon entering the state, pass through Campo, and make an interchange with US 160 south of Springfield.

At Baseline Road in Lafayette, SH 7 joins US 287 for about a mile, before it splits to the west on Arapahoe Avenue towards Boulder.

The road bypasses Berthoud en route to Loveland, where US 287 splits into the pair of one-way streets.

On the edge of the mountains, SH 14 splits and heads west into Poudre Canyon, while US 287 continues north into Wyoming.

The section of US 287 between Fort Collins and Laramie, Wyoming, carries very heavy truck traffic and is regarded as quite dangerous.

[2] Throughout 2012, the highway was expanded to three lanes north of Fort Collins, was resurfaced, and contained shoulders to prevent such accidents.