US 60 enters Missouri from Oklahoma south of Seneca and south of I-44. It is a two-lane highway. It intersects Route 43 at a roundabout south of Seneca. Next, US 60 intersects I-49 and US 71 at exit 24 before entering Neosho. I-49 has a concurrency with US 71. In Nesho, US 60 picks up a concurrency with Route 59. Route 86 has a brief concurrency with US 60 and Route 59. US 60 will turn east and leave Route 59 while Route 59 continues north at an interchange before passing through Granby. In Monett, US 60 intersects Route 37. After leaving Monett, US 60 from there to Republic has alternate passing lanes. US 60 bypasses Aurora to the south. Then, it passes through Marionville and enters the Springfield metropolitan area and picks up a concurrency with Route 413 before entering Billings. In Republic, US 60 becomes a four-lane divided highway and remains a four lane highway for the next 240 miles (390 km) until it reaches Charleston. US 60 enters Springfield and the concurrency with Route 413 ends. US 60 merges onto the James River Freeway where it has a brief concurrency with US 160 and Route 13. US 60 intersects US 65 known as the "Schoolcraft Freeway" before leaving Springfield and is also where the James River Freeway ends.
Between Springfield and Willow Springs, US 60 passes through various communities, most of them are mainly accessible by exits. US 60 also parallels the BNSF Railway tracks. US 60 intersects Route 125. It passes through Rogersville and Fordland before leaving Springfield metropolitan area. Afterwards, US 60 passes through Seymour. US 60 has a brief concurrency with Route 5 in Mansfield. US 60 passes through Mountain Grove. US 60 passes through Norwood and Cabool. Then, US 60 picks up a concurrency with US 63 east of Cabool. US 60 passes through Willow Springs where US 63 departs from US 60 at a freeway-to-freeway interchange east of Willow Springs. US 63 heads down southward to West Plains. At this point, US 60 no longer parallels the BNSF railway tracks as it heads down to West Plains as well.
US 60 passes through Mountain View where the divided highway briefly ends, While passing through Mountain View, US 60 has left turn lanes and has a concurrency with Route 17. After leaving Mountain View, US 60 goes back to a divided highway. US 60 passes through Birch Tree where it intersects Route 99. Then it passes through Winona where it has a concurrency with Route 19. US 60 passes through Chicopee, Van Buren and Ellsinore. Next, US 60 has a concurrency with US 67 until it enters Poplar Bluff as it leaves the Ozark Plateau.
In Poplar Bluff, US 60 will separate from US 67 at a cloverleaf interchange. After leaving Poplar Bluff, US 60 intersects Route 51 north of Fisk. Next, US 60 passes through Dexter then intersects Route 114 east of Morehouse. US 60 bypasses Morehouse US 60 then enters Sikeston where it intersects US 61 before intersecting I-55 exit 66 and I-57 exit 1 at a cloverleaf interchange. I-57 begins here, and US 60 picks up a concurrency with I-57. In Charleston, US 60 will leave I-57 at exit 12 and has a concurrency with US 62 and Route 77. At this point, US 60 becomes a two-lane highway. US 60 and 62 passes through Wilson City where Route 77 departs from US 60 and US 62. US 60 will leave Missouri crossing after the Cairo Mississippi River Bridge along with US 62 into Illinois.[1]
On May 17, 1946, William Jefferson Blythe, Jr., the biological father of Bill Clinton, died on US 60 in a car accident after he was tossed out of his vehicle and drowned in a ditch.[2]
There have been several improvements on US 60. The Missouri Department of Transportation (MoDOT) completed the process of upgrading 59 miles (95 km) of US 60 from Willow Springs to Van Buren to a four-lane highway (two lanes in each direction) on July 9, 2010, marking the completion of a continuous four-lane highway from Republic to Charleston, a total of approximately 240 miles (390 km).[3] Other improvement over the years involved replacing intersections with interchanges, adding frontage roads (outer roads), and many realignments of many parts of US 60.
West of US 60 and US 65 interchange in Springfield, there used to be railroad crossings over the BNSF Railway tracks that have been replaced with overpasses over the railroad tracks. That project included redesigning the US 60 and US 65 interchange. It was completed in 2012.[citation needed]
The portion of US 60 from Springfield to Sikeston was a consideration for the then proposed later cancelled Interstate 66 extension to follow.
In 2016, US 60 through Rogersville was converted into a freeway.[4] Spot improvements between Springfield and Rogersville was done.[5]