Big Creek is a stream in Iron and Wayne counties of the U.S. state of Missouri. It is a tributary of the St. Francis River. The stream headwaters are at 37°33′45″N 90°40′34″W / 37.56250°N 90.67611°W in Iron County and the confluence with the St. Francis is at 37°14′09″N 90°30′25″W / 37.23583°N 90.50694°WCoordinates: 37°14′09″N 90°30′25″W / 37.23583°N 90.50694°W in northern Wayne County.