The series begins in 2068. In the first episode, the crew of the Zero-X spacecraft are investigating the surface of Mars after mysterious radio signals are found to be coming from the planet. The source is discovered to be an alien city, which the astronauts fire on and destroy after mistaking a harmless surveillance device for a weapon. The city's inhabitants, the Mysterons, are sentient computers that form a collective consciousness. They are the remnants of the original Mysteron race: beings from another galaxy that maintained their colony on Mars for 3,500 years before abandoning the planet at the turn of the 20th century. The Mysteron computers use their power of "reversing matter" to rebuild their city before vowing revenge for the humans' unwarranted aggression.
Reversing matter, also called "retro-metabolism", enables the Mysterons to re-create people and objects as facsimiles that they can control. This ability is used to wage a "war of nerves" against Earth whereby the Mysterons issue threats against specific targets (from world leaders and military installations to cities and continents) and then destroy and reconstruct whatever instruments are needed (be they human or object) to carry out their plans. The presence of the Mysterons is indicated by two circles of green light that trail scenes of destruction and reconstruction. Although the Mysterons are able to influence events from Mars, their actions on Earth are usually performed by their replicated intermediaries.
Zero-X mission leader Captain Black becomes the aliens' primary agent when they seize control of his mind. Prior to the events of the series, Black was an officer of Spectrum, a worldwide security organisation that mobilises its personnel, vehicles and other resources to counter the Mysteron threat. Spectrum's most senior agents hold military ranks and colour codenames and are posted to the organisation's headquarters, Cloudbase – an airborne aircraft carrier stationed 40,000 feet (7.6 mi; 12 km) above the Earth's surface – where they answer to its commander-in-chief, Colonel White. Cloudbase is defended by Angel Interceptor fighters flown by a squadron of five female pilots codenamed Destiny (squadron leader), Harmony, Melody, Rhapsody, and Symphony. Spectrum also incorporates a fleet of armoured Spectrum Pursuit Vehicles (SPV), which are hidden in secret locations around the world, as well as patrol cars, hovercraft and machine-gun equipped helicopters.
Captain Scarlet becomes Spectrum's main asset in its fight against the Mysterons after the events of the first episode, in which the Mysterons attempt to assassinate Earth's World President as their first act of retaliation. The original Scarlet is killed in a road accident engineered by the Mysterons and replaced with a double under their control. However, after the reconstruction is shot by Spectrum's Captain Blue and falls to his death from a tower, he returns to life with the consciousness of the original Scarlet restored and is thereafter free of the Mysteron influence. Scarlet's new body possesses two extraordinary abilities: he is able to sense other Mysteron reconstructions nearby and, if injured or killed, returns to full health through retro-metabolism. Now able to use suicidally reckless tactics to thwart Mysteron plots, Scarlet repeatedly sacrifices himself in the knowledge that whatever his injuries he will return to face the Mysterons again.
Over the course of the series, it is discovered that Mysteron reconstructions are particularly vulnerable to electricity and can be detected by X-rays, to which they are resistant. Consequently, Spectrum develops two anti-Mysteron devices: the "Mysteron Gun" and "Mysteron Detector". A three-episode story arc focuses on the discovery of a Mysteron base on the Moon, its destruction by Spectrum, and Spectrum's efforts to negotiate with the Mysterons after converting the base's salvaged power source into an interplanetary communication device. A failed attempt to survey Mars, aborted military conferences and the sabotaged construction of a new Earth space fleet hinder Spectrum's progress in taking the fight to the Mysterons, and the organisation twice fails to capture Captain Black. In the penultimate episode, the Mysterons destroy Cloudbase with a fleet of spacecraft, but this is revealed to be a nightmare dreamt by a shot-down Symphony Angel. The final episode is a clip show that ends the series inconclusively with regard to the war between Earth and Mars.