Entering from Utah, I-70 descends into the Grand Valley where it meets the Colorado River, which provides its path up the western slope of the Rocky Mountains. Here I-70 serves the Grand Junction metro area before traversing more mountainous terrain. It passes through the 15 mile (24 km) section of I-70 through Glenwood Canyon, which was the last section of I-70 to be completed. This stretch was completed in 1992 and was an engineering marvel due to the extremely difficult terrain and narrow space in the canyon, which requires corners that are sharper than normal Interstate standards. Construction was delayed for many years due to environmental concerns. The difficulties in building the road in the canyon were compounded by the fact that a railroad occupied the south bank and many temporary construction projects took place to keep U.S. Route 6 open, at the time the only east-west road in the area. Much of the highway is elevated above the Colorado River. The speed limit in this section is 50 mph (80 km/h) due to the limited sight distance and sharper corners. Great care was taken to not destroy the local ecosystem with the building of the road. All rest areas through this stretch use reclaimed water.
The Eisenhower Tunnel, the highest vehicular tunnel in the world and the longest tunnel built under the Interstate program, passes through the Continental Divide. Because of the Eisenhower Tunnel's existence, I-70 is one of few roads connecting ski resorts such as Keystone and Aspen with Denver and it is more likely to be open than alternative roads. After traversing the mountainous terrain, I-70 goes through Denver and intersects Interstate 25. Leaving Denver, I-70 traverses through wide plains through east central Colorado before exiting into Kansas.
A section of the highway is displayed in the video game Syphon Filter 2 as an escape route for the protagonist.
Bicyclists are permitted to use the shoulder lane of I-70 in portions of Colorado; this is one of the few sections of Interstate Highway where non-motorized vehicles are permitted to use the road.
When leaving the Rocky Mountains, the Denver skyline can be seen on a clear day. This can fool truckers and other unsuspecting drivers because there is still over 10 miles of steep grade road before reaching the city. A series of signs warn truckers of the steep grade.