Over 100,000 years ago, the Talosians fought a nuclear war, leaving most of the planet's surface uninhabitable. They moved underground and developed their mental abilities to create realistic illusions, although their technological knowledge atrophied.
In 2236, the S.S. Columbia, a scientific survey ship from Earth, crashed on the planet. The Talosians retrieved the sole survivor, a human woman named Vina, and repaired her injuries, although their lack of knowledge of human anatomy hindered their efforts.
In 2254, the Talosians used a false distress signal to lure the USS Enterprise to Talos IV. They kidnapped Captain Christopher Pike in an effort to provide Vina with a mate. Pike and the Enterprise were eventually allowed to leave. Given the extreme threat of the Talosians' powers of illusion, Starfleet issued General Order 7, forbidding any travel to Talos IV, under penalty of death.
In 2257, Michael Burnham took her foster brother Spock to Talos IV in the hopes that the Talosians could heal him with their advanced mental abilities. The Talosians complied, but in return they demanded that Burnham share with them her memories of her estrangement from Spock. After some hesitation, Burnham willingly shared those memories, and the Talosians were able to heal Spock. (DSC episode: "If Memory Serves")
In 2267, Lieutenant Commander Spock kidnapped then-Fleet Captain Pike and hijacked the Enterprise to Talos IV. Given the specific circumstances, General Order 7 was rescinded, and Pike allowed to live the rest of his life with Vina and the Talosians. (TOS episodes: "The Cage", "The Menagerie")
By 2373, the Talosians became active participants in the so-called Telepathy War with the Dominion. Many Talosians were affected by the Meme Virus, as were many telepathic races within the Federation. Several Jem'Hadar invaded Talos IV, but Omega Squad, led by a telepathic recreation of Christopher Pike, helped repel the invasion. (SA comic: "Telepathy War")