An international crime syndicate known as Ghost uses terror, chemical and biological weapons, and political manipulation in its quest for world domination. Opposing them is Skyers 5, a covert team of special agents operating under the banner of the International Secret Police. The team is led by the professor and captain Kyousuke Maki, supported by members Polka, Yuri, Samson, and the young Taro Hayabusa, whose personal vendetta against Ghost stems from the syndicate murdering his family after he was caught in one of their schemes.

Equipped with advanced technology and a custom spacecraft, the team engages in high-stakes battles against Ghost's operatives, with the series blending science fiction scenarios with the stylized action of a Western gunslinger film. The original 1967 black-and-white run consisted of twelve episodes, followed by a color sequel series, Shin Skyers 5, which aired in 1971 and expanded the team's missions to a total of twenty-six episodes without altering the core premise or character roster.