Its boundary includes much of Covington (to the north) and portions of Kenton Vale and Fort Wright.

In 1919 the school moved to the mansion Holmesdale, built by Daniel Henry Holmes, who owned retail stores in Covington and New Orleans.

Holmesdale was used for a school cafeteria for a time, but was torn down in 1936 to make way for an administration building.

Its distinguished graduates include the mathematician Carl Faith, nuclear scientist Dick Lewis, Staples CEO Ron Sargent, Major League Baseball umpire Randy Marsh.

In 2009, the Holmes Bulldogs basketball team (boys) won its first state title.