The East and West branches both rise in West Marlborough Township, Pennsylvania, near the hamlet of Upland, and flow south through Kennett Square before uniting just north of the Delaware border.

The stream enters Delaware near the town of Yorklyn and flows southward through New Castle County, passing through Marshallton.

Ultimately, White Clay Creek enters the Christina River, also near Stanton.

[7] The Wilmington and Western Railroad follows the creek south from Yorklyn as far as Greenbank.

In the late 19th Century, several factories were located along Red Clay Creek, including those for the manufacture of flour, wool and iron.