Covington High School, the predecessor of Holmes High School, was established in 1853. In 1869, the first graduate, Miss Amelia S. Orr, received her diploma. Increased enrollment resulted in the construction of a high school building. Property at the corner of 12th and Russell was acquired and construction began. The cornerstone of the twelve-classroom, three-story brick building was set in place on October 25, 1872 with appropriate Masonic ceremonies.

By the early 1900s, excessive noise and dust from the nearby railroad tracks was causing problems for the school. In addition, the building was reaching its capacity. In 1914, the citizens of Covington passed a bond issue to construct a new Covington High School. A committee was appointed to select a site for the new school. On December 20, 1915, the committee announced that the 32-room Holmesdale Mansion and the surrounding 17 acres at Madison Avenue and 25th Streets had been purchased for $50,538.36. The home had been constructed by Daniel Henry Holmes, a wealthy department store owner in 1872.

A new forty-classroom high school was constructed on the Holmesdale site. The cornerstone of the building was set into place on November 27, 1916 and the new school was dedicated on January 6, 1919. A special feature of the building was a gymnasium measuring 100x50 feet. Soon after the dedication, the name of the school was changed from Covington High School to Holmes High School. The Holmes Mansion was used as a cafeteria, band room, offices and a bookstore.

In 1925, the school system financed the construction of a football stadium on the Holmes campus. The first home football game resulted in a victory for Holmes High School against Paris High School (52-0). In the following year, a new junior high school was constructed on the Holmesdale property. This building housed grades seventh through ninth and contained 42 classrooms, two domestic science rooms, two sewing rooms, a gymnasium, locker rooms, two art rooms and a large music room. Architects E.A. and C.C. Weber designed the three story brick structure. Enrollment for the 1927-28 school year increased to 714 pupils.

The old Holmesdale mansion was demolished in 1936 to make way for a new administration building. The Works Progress Administration provided funding for construction. By the end of the 1935-1936 school year, Holmes High School had awarded diplomas to 3,032 pupils (since the first graduation in 1869).
By the 1960s, the population of the City of Covington was in decline as residents moved to the suburbs. As a result, enrollment in the Covington Public Schools also declined. By the early 1980s, enrollment at the Covington Public Schools stood at 6,000 students, with 2,300 of these enrolled at Homes.

A more recent addition to the Holmes High School Campus is the David M. Evans Field House and Science Building. This complex was constructed in 1966 and included the largest high school gymnasium in Northern Kentucky. In 1980, a vocation school was constructed on the Holmes campus costing $2.7 million. The school was named in honor of Virginia Chapman, a longtime member of the Covington Board of Education. The Virginia Chapman Vocation School was eventually merged with Holmes High School in 2000.

The Covington School Board established the International Baccalaureate Program at Holmes High School in 1983. This rigorous academic program is aimed at the gifted students of the Covington Public School System (and surrounding systems).

Nordheim, Betty Lee, Echoes of the Past: A History of the Covington Public School System, 2002; Cincinnati Post, October 12, 1956, p. 38; Kentucky Post, January 14, 1919, p. 1, September 11, 1927, p. 5, September 20, 1927, p. 5 and June 17, 1983; Kentucky Times-Star, October 17, 1936; Homespun, September 28, 1936, p. 1..