U.S. Route 67 is a 1,560 mile (2,511 km) long north–south U.S. highway in the Central United States. The southern terminus of the route is at the United States-Mexico border in Presidio, Texas, where it continues south as Mexican Federal Highway 16 upon crossing the Rio Grande. The northern terminus is at U.S. Route 52 in Sabula, Iowa.

US 67 crosses the Mississippi River twice along its routing. The first crossing is at West Alton, Missouri, where US 67 uses the Clark Bridge to reach Alton, Illinois. About 240 miles (390 km) to the north, US 67 crosses the river again at the Rock Island Centennial Bridge between Rock Island, Illinois, and Davenport, Iowa. Additionally, the route crosses the Missouri River via the Lewis Bridge a few miles southwest of the Clark Bridge.

Throughout Texas, US 67 runs from north to south, in a primarily east–west manner, apparently violating the norms for numbering U.S. highways as odd-numbered routes are typically north–south in orientation, because prevailing north–south versus prevailing east–west designation is determined by the ultimate termini as the route traverses multiple states.[clarification needed]

US 67 is part of the La Entrada al Pacifico international trade corridor from its southern terminus to an intersection with U.S. Route 385 in McCamey, where the corridor follows US 385 to Odessa.

Between Dallas and Weaver, the highway runs concurrently with Interstate 30 (unsigned between Dallas and Royse City). From Weaver to Texarkana, US 67 runs parallel to I-30. The East of the Interstate 35E/Interstate 30 "mixmaster" in Downtown Dallas, U.S. Route 67 follows Interstate 30. West of the "mixmaster," U.S. Route 67 follows I-35E south through Oak Cliff. Along this portion, the U.S. Route 67 shield is also alongside the Interstate shield. Just north of Kiest Boulevard, U.S. Route 67 breaks off from Interstate 35E and maintains controlled-access ("Interstate grade") status down to Midlothian, where it becomes a four-lane divided highway to the western edge of Cleburne. Patrick CleburneThe route from Alpine to San Angelo was once a previous route of SH 99.

Though it passes through the heart of the Ozarks the highest mileage along US 67 is the last 150 miles between Fort Stockton and Presidio. Below Fort Stockton US 67 passes near the Glass Mountains, 6,535 ft. and the Sierra Del Norte range at 6,810 ft. West of Alpine US 67 passes near the Twin Sisters, 6,116 and 6,134 ft, Ranger Peak, 6,256 ft, and Paisano Peak, 6,091 ft. before going through Paisano Pass,5,180 ft. East of Marfa are views of Twin Mountains 6,681 and 6,910 ft, Goat Mountain, 6,642 ft, Cathedral Peak, 6,867 ft, and Cienega Mt. 6,565 ft. The Puertacitas Mountains, 6,350 and the Davis Mountains, 8,371 ft. can be seen from the Marfa Ghost Lights observatory to the north. The Davis Mountains are the highest elevation near US 67. Thirty miles south of Marfa US 67 reaches its highest point,5,428 ft. with Chinatti Peak, 7,732 ft. seen to the southwest.

In Arkansas, U.S. Route 67 runs parallel with Interstate 30 from Texarkana to Benton, where it then runs concurrent with I-30 to North Little Rock. It then runs on a freeway north to Highway 226 north of Newport, Arkansas where it goes back onto its original 2 lane alignment north to the border. In 2009, a bill was introduced to name the portion of U.S. Route 67 as "Rock 'n' Roll Highway 67." The bill, by Rep. J.R. Rogers of Walnut Ridge, designates U.S. 67 in Jackson, Lawrence and Randolph counties as "Rock 'n' Roll Highway 67." Besides Presley and Johnny Cash, the bill notes that Roy Orbison, Jerry Lee Lewis and Fats Domino also played at clubs along the stretch of highway.

Going from south to north, US 67 enters Missouri at the Arkansas state line. About 10 miles (16 km) north of the state line, it intersects US 160. At the southwest corner of Poplar Bluff, Business Route 67 goes into Poplar Bluff while US 67 bypasses Poplar Bluff to the west on a freeway-grade highway. It then joins US 60 at the northwest corner of Poplar Bluff. Both 60 and 67 then follow a four-lane route to an interchange about 6 miles (9.7 km) northwest of Poplar Bluff, where US 60 heads west toward Springfield while US 67 heads north to St. Louis.

Construction is complete to divide the highway through Wayne, Madison and Butler Counties, including bypasses around Greenville and Cherokee Pass. The new divided highway opened on August 19, 2011, with a ribbon-cutting ceremony. Dividing the highway from the Poplar Bluff bypass south to one mile past US 160 is proposed by MoDot.

From Fredericktown, US 67 passes through Farmington, Park Hills, Desloge, and Bonne Terre. About 25 miles (40 km) north of Bonne Terre, US 67 crosses Interstate 55 and enters Festus and Crystal City and picks up US 61. This becomes known as Jeffco Boulevard from that point until it exits Jefferson County and enters St. Louis County as Lemay Ferry Road.

When US 67/61 reaches St. Louis County, It travels Lemay Ferry Road (Route 267) until it reaches Lindbergh Boulevard. There it travels Lindbergh Boulevard (known as Kirkwood Road in Kirkwood). Us 61 then turns west onto I-64/US 40 West towards Wentzville. Lindbergh, named for aviator Charles Lindbergh, continues north through Frontenec, Ladue, Creve Coeur, Maryland Heights, Bridgeton, Hazelwood and Florissant until it reaches Lewis & Clark Boulevard (Route 367). From there, it continues straight north to West Alton, Missouri and then crosses the Mississippi River on the Clark Bridge and enters Alton, Illinois.

The only vehicular tunnel in Missouri is located on US 67 at Lambert-St. Louis International Airport, where the road tunnels under the runway.

In the state of Illinois, U.S. 67 runs north from the Clark Bridge in Alton through the Forgottonia region of western Illinois. It runs near the cities of Jacksonville, Beardstown, through Macomb, and near Monmouth before crossing into Iowa across the Rock Island Centennial Bridge.

U.S. 67 enters Iowa in Davenport. It follows an alignment through Bettendorf and Clinton which parallels the Mississippi River. Near Sabula, U.S. 67 meets U.S. Route 52 and ends.

US 67 is one of the older US highway corridors in Madison County, Missouri. The northern terminus of US 67 was in Missouri under the original US highway numbering scheme of 1926, likely due to limited bridge crossings over the Mississippi and Missouri Rivers. In Missouri, US 67 replaced Route 23, created in 1922 from Arkansas to Fredericktown. By 1932, with a Mississippi River crossing route determined, US 67 was extended north along Illinois Route 3 to Rock Island, Illinois.

Even though the old Clark Bridge had been opened to traffic across the Mississippi River at Alton in 1928, US 67 originally crossed the Mississippi River with US 66 via the McKinley Bridge from St. Louis to Venice. From Venice, US 67 headed north along what had been IL 3 via Alton to Rock Island, Illinois. The original route of IL 3 from Alton to Jacksonville that became US 67 went through East Newbern, Jerseyville, and Carrollton.

US 67 had several routes over the years. The Illinois section was likely not included in original US highways in 1926, due to limited bridge crossings. The history of US 67 through Illinois is almost as storied as the famous highway to its east U.S. Route 66 that follows the old Illinois Route 4.

The northern terminus was at Alt. US 61 near Fredericktown, Missouri, in 1926. The route was extended north on Illinois Route 3 (through western Illinois) to its northern terminus in Rock Island, Illinois by 1932 . Sometime after 1940, US 67 was routed into Madison County. Then, it was co-signed with Route 66 as both routes went across the McKinley Bridge.

By the mid-1940s, US 67 had been rerouted from St. Louis to Alton via the Lewis Bridge over the Missouri River and the Clark Bridge (formerly the Old Clark Bridge) over the Mississippi River. The Alton to Jerseyville section now passed through Godfrey and Delhi. By the mid-1950s, a more direct route for US 67 from Godfrey to Jacksonville via Greenfield had opened. Heading north from Downtown Alton, US 67 was rerouted via an abandoned railroad grade to the north end of town.

Between Fort Bellefontaine, Missouri (near Lewis Bridge) and south of St. Louis, US 67 followed two different routes. US 67 originally followed Lewis and Clark Boulevard, Florissant Avenue, 7th Street, and Broadway south through St. Louis. US 67 Bypass followed Lindbergh Boulevard around the city. Route 99 was an inner bypass within the city limits, following Kingshighway Boulevard and Riverview Boulevard between Route 30 (Gravois Road) and US 67 (Florissant Avenue). US 67 replaced Route 99 in the mid-1950s, using Loughborough Avenue at the south end, and the old route south of downtown became an extension of US 67 Alternate, which had begun downtown and crossed into Illinois towards Alton. (The old US 67 north of downtown was mostly US 66 City.) Later, in the late 1960s, US 67 moved to the bypass, and the old route, where not turned back to the city, became Route 267 and Route 367.

In 1962 another reroute occurred, due to the completion of a new river bridge over the Illinois River at Beardstown. A new direct route was constructed from this bridge at Beardstown to Rushville, eliminating the earlier US-67 eastern route northeast along current IL-100 to Frederick then turning north to Rushville. A western by-pass of downtown Rushville was completed a couple of years later.

In 1964, US 67A was replaced by Route 3, as St. Louis started to get rid of highways such as 67A. A new four-lane Route 3 opened a few years later.

In 1968, US 67 was rerouted on a more western route between Jacksonville and Beardstown. The route was the existing IL-104 (Jacksonville to near Merodosia) and IL-100 (Near Merodosia to Beardstown). The original US 67 road passed through Virginia on what is now IL-78 (Jacksonville to Virginia) and then on IL-125 (Virginia to Beardstown), which follows the historic post road between Springfield and Beardstown.

Before 1994, US 67 went through Alton on Belle Street and crossed the river by the Colonial Bread store. After 1994, US 67 got a new bridge as well as a new route through Alton. In the summer of 1994, parts of the road were blown up in a span of 8 to 10 weeks. Today, planners from Godfrey and Jerseyville are talking about building a new US 67 that would take a western route along the current IL 267.

When US 67 was shifted to a more direct route north of Alton between Godfrey and Jacksonville by the mid-1950s, the old route via Jerseyville and Carrollton became Alt US 67. This designation lasted until around 1965 when the route became IL 267.

In 2001, IDOT rerouted US 67 back onto the original (1940) routing (western route) north of Alton to Murrayville and IL-267 was put onto the newer alignment (eastern route) from near Murrayville through Greenfield to Medora. South of Medora to Godfrey the road retained only IL-111, a second number on this section. The rerouting was to accommodate a future "Corridor 67" expressway that will be built within the next decade or so. IDOT construction began in 2004 near Jacksonville. The new expressway is supposed to follow the corridor through White Hall, Carrollton, and Jerseyville and will eventually end in Godfrey.

From Macomb north to Monmouth, US 67 is currently a "Super Four" 65 mph (105 km/h), 4 lane highway. The Roseville Bypass was completed in 2003.

U.S. Route 167 is the only auxiliary route of US 67. US 167 stretches from Abbeville, LA to Ash Flat, AR and intersects US 67 at Bald Knob, AR.

US 67 has numerous business routes in Texas, Arkansas, Missouri, and Illinois.