It runs for approximately 20 miles (32 km) north–south entirely within the urbanized environment of the Denver Metropolitan Area.

On its southern end, it begins at U.S. Route 285 (US 285) in Cherry Hills Village, just south of the Denver city limits in Arapahoe County.

It intersects SH 83 near Cherry Creek and then US 40, US 287, and Interstate 70 Business (also known as Colfax Avenue) east of downtown Denver.

It then merges with US 6 and US 85 through Commerce City, until it branches off from US 6 and US 85 to the northeast, passing along the northwest boundary of the Rocky Mountain Arsenal National Wildlife Refuge.

It then followed various streets northeast along US 85 north to Greeley, where it turned abruptly eastward along US 34 to US 6, where it continued to Sterling and finally along US 138 to the Nebraska border.