Route 163 begins at an interchange with US 63 and State Route H, with the latter leaving the interchange at the opposite side from Route 163. The highway then runs north parallel to US 63. This section was originally part of US 63 before being bypassed in 2011 and is now known locally as Tom Bass Road. Route 163 originally began at an at-grade intersection before being removed when a new US 63 southbound lane was built. After two miles (3.2 km) running parallel to US 63, Route 163 turns west and then passes in a northwesterly direction through Rock Bridge State Park. It briefly leaves the park to pass through the village of Pierpont, where Route N is intersected. After leaving the park, Route 163 turns north upon its intersection with Route K. North of the Route K intersection, the route enters the city of Columbia, through which the road is known locally as Providence Road. After entering Columbia, the route gains four-lane divided highway status, and then immediately passes Rock Bridge High School, one of four public high schools in the city. North of the school, the highway intersects Route AC, which is known locally as Nifong Boulevard. After crossing Hinkson Creek, Route 163 passes near the University of Missouri sports complex, including Faurot Field and the Mizzou Arena. Near the complex, the route loses its median barrier and crosses Route 740, also known as Stadium Boulevard. Route 163 then passes through Downtown Columbia. In the southwest corner of the intersection with Business Loop 70 lies Hickman High School, another public high school. Just north of Business Loop 70 is the route's northern end at I-70/US 40.

The entire route is in Boone County.

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