The earliest settlements by Europeans in the area were built in the form of stations, or forts, along the banks of the creek.

Following the construction of the U.S. Army base at Bowman Field in 1940, it was found that the area's limestone was causing septic tanks in Seneca Gardens to malfunction and wash raw waste into the creek.

Weicher Creek flows from the Hurstborne Area, and the Sinking Fork has its headwaters near Anchorage, Kentucky.

They join in St. Matthews and flow through Cherokee Park until it meets the South Fork near the Bourbon Stockyards.

The Muddy Fork rises at a stone springhouse in Windy Hills and runs parallel to the Ohio River and was rerouted during the construction of Interstate 71.