Route 19 is a long state highway in Missouri. Its northern terminus is at U.S. Route 61 in New London and its southern terminus is at U.S. Route 63 on the north side of Thayer. Route 19 is one of Missouri's original 1922 highways, though it initially had a northern terminus at Route 14 (now Interstate 44) in Cuba and was later extended north.

Missouri route 19 begins at U.S. Highway 61 in New London. It then travels mainly south, forming an 8 mile concurrency with U.S. Highway 54, 3 miles west of Farber. The highway intersects Interstate 70 near New Florence. It crosses the Missouri River on the Christopher S. Bond Bridge bridge at Hermann. There is a concurrency with Missouri Route 100 through Hermann. It then forms an extremely brief 1 mile concurrency with U.S. Highway 50 at Drake. Through Owensville there is a concurrency with Missouri Route 28. The highway intersects Interstate 44 at Cuba. South of Cuba, the highway is designated as a scenic highway. It forms a concurrency with Missouri Route 8 through Steelville. It passes through the Ozark National Scenic Riverways and portions of the Mark Twain National Forest. The highway overlaps U.S. Highway 60 in Winona and U.S. Highway 160 in Alton. The highway terminates at U.S. Highway 63 in Thayer.

The part from Drake north to US 54 east of Mexico was Route 45 from 1922 until about 1930.