In October 1965, Smithsonian Astrophysical Observatory (SAO) Director Fred Lawrence Whipple visited the southwestern United States for the purpose of choosing a site for a new branch observatory. The location selected was Mount Hopkins in the Santa Rita Mountains of Arizona. Development of the site began in 1966, and the observatory was officially opened on October 23, 1968. Research activities at Mount Hopkins included optical and laser satellite tracking for geodetic and geophysical studies, spectroscopic observation of both stellar and planetary bodies, and gamma-ray astronomy.

During 1965 and 1966, the Mount Hopkins Observatory project was administered by the Office of the Director. Jack A. Coffey served as the first Project Administrator from December 1965 to December 1966 (except during March and April 1966, when Raymond Watts served in the position). In 1967, the newly created Programs Management Office assumed responsibility for Mount Hopkins, with John J. Burke as Chief Administrative Officer. In 1969, the Mount Hopkins Department was established, with Ronald R. LaCount as Manager. Charles Tougas was appointed Field Manager of the Mount Hopkins site in 1966. He was assisted by Werner Kirchhoff, who served as Special Technical Advisor.