U.S. Route 66 in Missouri ran from downtown St. Louis at the Mississippi River to the Kansas state line west of Joplin. The highway was originally Route 14 from St. Louis to Joplin and Route 1F from Joplin to Kansas. It underwent two major realignments (in the St. Louis and Joplin areas) and several lesser realignments in the cities of St. Louis, Springfield, and Joplin. Current highways covering several miles of the former highway include Route 100, Route 366, Route 266, Route 96, and Route 66. Interstate 44 approximates much of US 66 between St. Louis and Springfield.
Missouri was the first state to erect a historic marker on US 66. It is located at Kearney Street and Glenstone Avenue in northeast Springfield. A new marker, designating the highway as a National Scenic Byway, was erected May 5, 2006. The historic alignment in Missouri is marked based on the route in 1935.
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The original route through St. Louis entered Missouri on the McKinley Bridge in St. Louis and continued west on Salisbury Street, turned south on Florissant Street, then west on Manchester Road (Route 100). It joined the later alignment at Gray Summit.
The first major re-alignment of US 66 involved the construction of Watson Road (now Route 366). The road was realigned down Chippewa Street and Watson Road. Interstate 44 was built down Watson Road for several miles west of Sunset Hills. With this realignment, US 66 crossed the Mississippi on MacArthur Bridge. The older highway passes through downtown Pacific in a scenic area under steep bluffs.
Bypass US 66 was routed over the Mississippi on the north side of St. Louis via the Chain of Rocks Bridge. This alignment is now an outer road of Interstate 270 from the river to Lindbergh Boulevard (U.S. Route 61/U.S. Route 67), then south on Lindbergh to Watson Road. At other times, US 66 crossed the Mississippi on the Martin Luther King Bridge, and on the Poplar Street Bridge.
The highway passes near Meramec Caverns in Stanton, formerly a famous stop. Between Sullivan and St. James is a major grape growing area and many wineries.
Cuba, known as Route 66 Mural City has 12 outdoor murals and other art and sculpture throughout the town and along the Route 66 corridor. Its restaurants are often a "must stop" for Rt. 66 travelers. The Crawford County History Museum has a Route 66 exhibit.
At Rolla, about halfway to Springfield, US 66 intersects U.S. Route 63 and passes the Missouri University of Science and Technology. The university's half-scale model of Stonehenge is located next to the highway. At Rolla, US 66 entered the Ozark Mountains. At Philipsburg, Interstate 44 was built some distance away from former US 66 and passed through Marshfield, birthplace of astronomer Edwin Hubble.
The alignment through Springfield includes Kearney Street, Glenstone Avenue, St. Louis Street, College Street, and Chestnut Expressway. At Springfield, US 66 was joined with U.S. Route 65 for several miles, and also served as the original western terminus of U.S. Route 60. US 60 no longer intersects US 66 in Missouri at all. Bypass US 66 followed Kearney Street on the north side of Springfield to West Bypass. Later, this would become the main alignment of US 66.
Springfield boasted the only double-bannered highway: Alternate Business US 66.
Among the Route 66 sites in Springfield are the Abou Ben Adhem Shrine Mosque and the site of Red's Giant Hamburgs, the world's first drive-thru restaurant.
West of Springfield, US 66 followed Route 266 and Route 96. Interstate 44 turned southwest at Halltown, away from US 66. The reason for this was the already completed Will Rogers Turnpike in Oklahoma, which Oklahoma wished to become part of Interstate 44. In order to complete the hookup, I-44 took over for U.S. Route 166 from Mount Vernon to the Oklahoma state line southwest of Joplin. At Carthage, Historic US 66 winds through various county roads and the city streets of Carterville and Webb City. In Carthage, US 66 once ran concurrently with U.S. Route 71.
Due to the mining history of Joplin, the realignment of US 66 in Joplin was partially for traffic and partially because of cave-ins of mines built under the highway. It zig-zagged through the city, following Rangeline Road, Zora Street, Florida Avenue, Utica Street, Euclid Avenue, St. Louis Avenue, Broadway, Main Avenue, and Seventh Street, the last now State Route 66. An old segment of highway (named Route 66 Boulevard), splits off from modern Route 66 and enters Kansas to the north of the current highway.
Later, US Route 66 went straight south on Rangeline to Seventh and then west to the Kansas state line.
With the completion of Interstate 44, US 66 was aligned down I-44 from St. Louis to Halltown, except for the St. Louis area itself, where it continued on Gravois Road (Route 30) and Chippewa Street/Watson Road (Route 366). At Halltown, US 66 continued down what would later be Route 96 to Joplin. When Interstate 55 in Illinois was completed in 1979, US 66 was truncated to east of Duenweg. Seventh Street, east of Duenweg, had been US 166, then now US 66 which continued straight through Duenweg, Duquesne, and Joplin to the Kansas state line.
In 1922, US 66 was originally Route 14, connecting St. Louis and Joplin. In 1926, it was designated a national highway, US 66.
The route between St. Louis and Springfield is an old road. It had traditionally been a Native American trail, known as the "Osage Indian Trail". By the early-to-mid-19th century, settlers laid a telegraph line along the road (it continued south from Springfield to Fort Smith, Arkansas). It then was called the "Wire Road", and later the "Old Wire Road" after the telegraph line came down.
The highway subsequently became part of the Ozark Trail.
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