Producer Quinn Martin developed the series as a replacement for the hugely popular The Fugitive, which was ending its run in 1967.

Creator Larry Cohen had previously conceived two similar series: Branded (1965), about a soldier seeking to prove his valor, and Coronet Blue (1967), about an amnesiac man pursued by a mysterious group.

The show was inspired by 1950s 'alien Doppelgänger' films such as Invasion of the Body Snatchers and Quatermass 2, though Quinn Martin mainly wanted a premise that kept the hero on the move and unable to go to the authorities.

Larry Cohen said the series' concept owed more to Alfred Hitchcock films like The 39 Steps, Saboteur, and North by Northwest—stories where the hero alone knows about a conspiracy and no one believes him—than to The Fugitive, despite obvious similarities to that show.

The aliens' flying saucers were designed to resemble 1950s UFO photographs by self-proclaimed contactee George Adamski, but with five shallow protrusions instead of three spheres underneath, and much of their technology used a distinctive five-sided 'penta' design.

The production crew deliberately designed the Invaders' technology, sets and control panels to look utterly alien and unlike conventional human equipment, a design philosophy later echoed by H. R. Giger's work on Alien.

Because ABC was the last network to fully adopt color broadcasting, each episode opened with an 'in color' promo bumper announcing 'Next... The Invaders, In Color!'

The pilot episode 'Beachhead' was remade in 1977 as 'The Nomads' for another Quinn Martin series, Quinn Martin's Tales of the Unexpected, starring David Birney.

A 1995 four-hour Fox miniseries revival, also titled The Invaders, starred Scott Bakula as a new protagonist, with Roy Thinnes making a brief appearance as an aged David Vincent passing on his mission.

The series was especially popular in France, where it was broadcast and rebroadcast from 1969 into the 2000s, and Roy Thinnes was invited to a Paris screening of episodes in 1992.

In Hungary, where several episodes aired in 1980 under the title 'Támadás egy idegen bolygóról,' newspaper critics dismissed the show as 'more fiction than science,' though it remained popular with viewers.