U.S. Route 36 is an east–west United States highway that runs for 1,414 miles (2,276 km) from Rocky Mountain National Park, Colorado to Uhrichsville, Ohio. The highway's western terminus is at Deer Ridge Junction, an intersection in Rocky Mountain National Park, Colorado, where it meets U.S. Route 34. Its eastern terminus is at U.S. Route 250 in Uhrichsville, Ohio.

US Route 36 begins at US 34 at Deer Ridge Junction in Rocky Mountain National Park in Colorado, just west of Estes Park. It then passes through Boulder and Denver on its way to Kansas. Between Boulder and Denver, the road that is now US 36 was originally built as the Denver-Boulder Turnpike. It serves today as a major arterial freeway in the Front Range Urban Corridor. Between Denver and Byers, US 36 exists in unsigned overlaps with I-270 and I-70, while some parts of its original route are signed separately as Colorado State Highway 36. After it diverges from I-70 in Byers, US 36 is a relatively lightly-traveled two-lane rural highway to the Kansas state line.

US-36 passes through all 13 counties in Kansas which border Nebraska. The highway enters the Sunflower State from Colorado in Cheyenne County and shares a 7-mile (11 km) concurrency through the town of St. Francis with K-27, the first north–south route intersected in Kansas. K-27 splits east of St. Francis and heads south toward Goodland, and US-36 then continues through Bird City and McDonald before intersecting K-25 in Atwood, the seat of Rawlins County.

US-36 continues east through Decatur County, intersecting with US-83 in Oberlin before beginning a concurrency with K-383 in Norton County, a concurrency which runs for 12 miles (19 km) through the city of Norton, where it crosses US-283. K-383 splits in eastern Norton County and bends northeast toward Almena and the Nebraska state line, while US-36 enters Phillips County, picking up a brief concurrency with US-183 in Phillipsburg.

The highway passes through the small towns of Agra and Kensington before reaching Smith Center, the seat of Smith County, where US-281 joins US-36 for a 12-mile (19 km) concurrency. Near Lebanon, US-36 passes about 4 miles (6.4 km) south of the Geographic center of the contiguous United States, which is indicated by a marker where US-281 splits northward to Lebanon. The road then passes through largely unpopulated areas, except for the tiny town of Mankato in Jewell County.

At Belleville, the seat of Republic County, US-36 intersects US-81, a four-lane expressway which heads south toward Concordia and Salina, where it becomes Interstate 135 and continues south toward Wichita. After passing through Washington County, US-36 picks up brief concurrencies with US-77 in Marysville, the seat of Marshall County, and with US-75 in Fairview.

In Hiawatha, the seat of Brown County, US-36 intersects the concurrency of US-73 and US-159, before entering Doniphan County for its final trek through the state, passing through Troy, Wathena and Elwood before crossing the Missouri River on the Pony Express Bridge and entering Missouri.

The section of US-36 from Washington, Kansas to St. Joseph, Missouri is officially called the Pony Express Highway because it marks the starting section of the Pony Express. It crosses the Missouri River on the Pony Express Bridge. From the western junction with K-383 to the Missouri state line, US-36 is part of the National Highway System.

Except for wider sections in towns and passing lanes on hills, US-36 through Kansas is mostly a two-lane surface road. However some of the principal intersections all along the road are grade-separated diamond interchanges. From the Little Blue River just west of the K-148 junction to the US-77 North junction just west of the Big Blue River at Marysville, US-36 is a four-lane divided surface highway. From Hiawatha to west of Wathena, the road is a two-lane freeway. After passing through Wathena as a surface street, it becomes a four-lane freeway to the Missouri state line.

US 36 in Missouri passes through or near St. Joseph, Cameron, Chillicothe, Brookfield, Macon, Monroe City and Hannibal. It was Route 8 from 1922 to 1926.

On August 3, 2005, residents of Macon, Marion, Monroe, Shelby, and Ralls counties approved Proposition 36B, which excludes Ralls County from the Transportation Development District and allows for the construction of a 4-lane US 36 to be constructed without Ralls County's participation. This construction would serve as an extension of Interstate 72 west from Hannibal to Cameron and would make US 36 four lanes across Missouri.

All of US 36 in Missouri is named the V.F.W. Memorial Highway. The section from St. Joseph to Hannibal parallels the route of the Hannibal and St. Joseph Railroad, which was the reason St. Joseph was selected for the Pony Express. The two towns were the second and third largest cities in the State of Missouri prior to the American Civil War. Prior to the establishment of the railroad in the late 1850s, the stagecoach route was called the "Hound Dog Trail."

For the Missouri portion of the highway, MoDOT has completed their recent project, upgrading to a four-lane divided highway across the state.

With the passage of Proposition 36B, the US 36/I-72 Corridor Transportation District was created to help fund construction to convert the remaining 38 miles (61 km) of 2-lane highway between Macon, Missouri and Monroe City, Missouri by September 30, 2010. East of the Monroe City exit, US 36 is a 4-lane highway to US 61, where I-72 takes over the alignment.

In the state of Illinois, U.S. 36 runs concurrent with much of Interstate 72. It enters from Missouri across the Mississippi River on the Mark Twain Memorial Bridge, and runs east, crossing Interstate 55 in Springfield. At the U.S. Route 51 bypass in Decatur, U.S. 36 leaves I-72 and runs due east through downtown Decatur. U.S. 36 then continues east, through Tuscola and several smaller communities, all the way to the Indiana border.

US 36 enters Indiana near Dana in Vermillion County. It then passes through the towns of Montezuma, Rockville, Bainbridge, Danville, and Avon before entering Indianapolis. The original route through Indianapolis consisted of Rockville Rd., Washington St.. West St./Michigan Rd. (Now Dr. Martin Luther King St.) 38th St. and Pendleton Pike. However, US 36 is now concurrent with Interstate 465 south of Indianapolis. East of The Circle City, US 36 travels northeast through Lawrence, McCordsville, Pendleton, Losantville, Modoc, and Lynn before exiting into Ohio.

US 36 enters Ohio in Darke County near the small village of Palestine, Ohio. In Ohio it travels through Darke, Miami, Champaign, Union, Delaware, Knox and Coshocton Counties before reaching its terminus at Uhrichsville in Tuscarawas County. It conjoins with US Route 127 in Greenville for about 5 miles (8.0 km). It also conjoins with US Route 33 in Marysville for about 5 miles (8.0 km).