[1] It is in the Saint Lawrence River drainage basin, is a left tributary of the Mississippi River, and was named after the River Clyde in Scotland.

The Clyde flows south from its source at the outflow from Clyde Lake in geographic Lavant Township[2] in the municipality of Lanark Highlands to the community of Clyde Forks, where it takes in the right tributaries Middle Branch Clyde River and South Branch Clyde River.

To this point, the river is paralleled by the K&P Rail Trail which follows the course of the former Kingston and Pembroke Railway.

The river then heads east, then southeast into geographic Darling Township[3] then geographic Lanark Township,[4] takes in the right tributary Little Clyde River, and arrives at the community of Lanark.

The river continues south passing briefly through geographic Drummond Township[5] in the municipality of Drummond/North Elmsley, then reaches its mouth at the Mississippi River in geographic Bathurst Township[6] in the municipality of Tay Valley, north of the town of Perth.