US 65 enters Missouri between the towns of Omaha, Arkansas and Ridgedale, Missouri. The road is a four-lane expressway, traveling through both Branson and Hollister towards Springfield. Through the Branson area, it is a freeway. North of Branson, the highway intersections with both westbound Route 76 and U.S. Route 160. All the way to Highlandville, U.S. 160 is the old alignment of U.S. 65. Just south of Route EE at the Highlandville exit, U.S. 65 returns to freeway status. The freeway is called "Schoolcraft Freeway" in Springfield, named in honor of Henry Rowe Schoolcraft. Also in Springfield, the highway has junctions with U.S. Route 60 and Interstate 44. The I-44 interchange includes a flyover ramp connecting northbound U.S. 65 with westbound I-44. Construction is completed that added two at U.S. 60. In September 2011, U.S. 65 became a six-lane divided freeway in Springfield between Interstate 44 and U.S. 60. It was the first six-lane highway in Southwest Missouri. North of Springfield, it returns to a four-lane, non-interstate highway. From Springfield to Buffalo, U.S. 65 has been upgraded as a four-lane non-interstate highway. This project began with the addition of a partial four-lane highway through the Fair Grove area to replace a dangerous traffic light intersection with an overpass. It culminated with the entire length of U.S. 65 becoming a four-lane highway from Springfield to just outside of Buffalo. The project was completed in summer 2010. Through Buffalo, the highway now becomes two lanes with a center left-turn lane. This part of the highway has also seen upgrades in recent years, such as adding rumble strips and extending the middle turn lanes to just outside the city's northern portion. From Buffalo to Preston, entering Hickory County, U.S. 65 remains a two-lane highway and has a four-way intersection with U.S. Route 54. At Warsaw, the highway crosses over the western end of the Lake of the Ozarks and again becomes a four-lane non-interstate highway at the intersection with Route 7. At Sedalia, it has an intersection with U.S. Route 50. At Marshall Junction, north of Sedalia in Saline County, U.S. 65 intersects with both Interstate 70 and U.S. Route 40. In Marshall, U.S. 65 returns to two-lanes and stays so all the way up to Iowa. At Waverly, the highway becomes concurrent with U.S. Route 24. Also in Waverly, U.S. 65 and U.S. 24 both cross the Missouri River on the Waverly Bridge. Further north, the road crosses U.S. Route 36 at Chillicothe and U.S. Route 136 at Princeton. The highway leaves Missouri at South Lineville and enters Iowa. The section of highway from Preston to Marshall Junction has been cited as a good drive for motorcyclists, with its sparsely populated areas and the hilly landscape.
History
From 1922 to 1926, US 65 in Missouri was known as Route 3. US 65 originally followed Route 248 and US 160 between Branson and Springfield. Route 3 was originally planned on a shorter route between Springfield and Preston, with Route 71 on the longer alignment via Buffalo, but Route 3 was quickly shifted east, absorbing Route 71.