Cameron Run becomes Hunting Creek and empties into the Potomac River just south of the Woodrow Wilson Bridge.

In 1913–1915 the Alexandria Water Company built a dam on Holmes Run in order to create Lake Barcroft as a potable water reservoir for Alexandria.

In the early post-war era, Alexandria began to exceed the capacity of Lake Barcroft and in 1949 discontinued its use in favor of Occoquan Reservoir.

As an urban river, Holmes Run has in places been heavily channelized, but also significant portions have been developed as urban greenspace as Holmes Run Trail.

Above Lake Barcroft its route makes up the border of West Falls Church and Annandale.