Centennial High School started out as a 16 x 20 foot structure built in 1873 at 421 North Santa Fe Avenue in what became downtown Pueblo.

Six years later, a larger adobe building went up at Eleventh and Court Streets on Pueblo's north side.

This building served for over fifty years until a new campus was built further north at Mountview Drive and Baltimore Avenue in 1973.

A museum featuring a recreation of the font facade from the original building was built on campus, and it houses archival material detailing the history of the school and serves as the headquarters for the Centennial's alumni organization.

Well-known graduates of Centennial include David Packard (1930), co-founder of the Hewlett-Packard Company; Morey Bernstein (1937), author of The Search for Bridey Murphy; Edra Jean "E.J."