Hermesprota Creek begins in the Har Zion Cemetery near the community of Collingdale, Pennsylvania.

It flows south-southeast for several tenths of a mile before passing under U.S. Route 13 and turns west and enters Sharon Hill, Pennsylvania.

The creek turns south and enters the communities of Darby Township and Folcroft.

Hermesprota Creek then enters the John Heinz National Wildlife Refuge and receives two small unnamed tributaries, from the right and left banks respectively.

A concrete arch bridge with a length of 30.8 feet (9.4 m) carries Folcroft Avenue over the creek and was built in 1925.