The headwaters of the Gasconade are in the southeastern corner of Webster County northeast of Seymour, Missouri where it drains the eastern margin of the Springfield Plateau at approximately . The river joins the Missouri River at the city of Gasconade at . The river follows a meandering course through the Ordovician age dolomite and sandstone bedrock of the Ozark Salem Plateau creating spectacular bluffs and incised meanders along the way. Numerous springs and caves occur within the drainage area and along the river course. Significant tributaries include the Osage Fork of Webster and Laclede counties and Roubidoux Creek and Big Piney River of Texas and Pulaski counties. The Roubidoux and Big Piney flow respectively along the west and east boundaries of Fort Leonard Wood which lies a short distance south and east of the Gasconade.