Twelvemile Creek is a stream in Madison County in the U.S. state of Missouri. It is a tributary of St. Francis River.
Part of the course of Twelvemile Creek lies 12 miles (19 km) from Fredericktown, hence the name.
Coordinates: 37°22′20″N 90°27′23″W / 37.372274°N 90.456506°W