With the onset of the Cold War and the threat of long-range Soviet nuclear bombers, the Guard wrote a new page in its long history of homeland defense. Beginning in 1954, thousands of Army Guardsmen manned antiaircraft artillery positions across the country, adopting for the first time a Federal mission while in a State status. In the late 1950s, the Guard began transitioning from guns to the longer-ranged and more lethal missiles. For exactly sixteen years, from September 14, 1958 to September 14, 1974, the Army National Guard manned Nike-Ajax and Nike-Hercules missile batteries in an operational status. At the height of the program in 1969, seventeen states (California, Connecticut, Hawaii, Illinois, Maryland, Massachusetts, Michigan, Missouri, New Jersey, New York, Ohio, Pennsylvania, Rhode Island, Texas, Virginia, Washington and Wisconsin) provided more than 7,000 soldiers to man 54 missile batteries around sixteen key metropolitan areas.

The Hawaii National Guard's 298th Artillery Group was the first National Guard unit to adopt the Nike-Hercules missile, becoming operational on-site in early 1960. Hawaii was also the only state to man all of its firing batteries with Guardsmen; in the continental United States the Guard manned about a third of all Nike sites. While the rest of the Nike force conducted its annual practices at McGregor Guided Missile Range in New Mexico, the Hawaii Guard was unique in that it conducted its annual live-fire certifications from mobile launchers firing off the north shore of the island of Oahu. It was during just such a live-fire that Battery B, 1st Missile Battalion, 298th Artillery Group recorded the longest successful Nike-Hercules missile intercept of a target.

The advent of Intercontinental Ballistic Missiles led to major cutbacks in the Nike program in 1971 and its termination in 1974. Though no missile was ever fired in anger, the duty encompassed a 24 hour watch, 365 days a year, and thousands of alerts. Guardsmen had demonstrated their ability to conduct real-world missions while in a part-time, state-controlled status, in the process proudly adopting for themselves the title "Missile-Age Minutemen."