In 2293, Khitomer was selected as the neutral venue to host the Klingon-Federation peace talks following the Praxis incident. At the time, none of the major Alpha Quadrant powers seemed to have staked a claim to the planet.
By 2346, Khitomer was home to a Klingon colony of around 4000. At this point in time the Romulans were officially allied with the Klingon Empire, yet using the cover of this alliance to weaken the Empire through sneak attacks. One of these hit Khitomer, aided by the traitor Ja'rod allowing the Romulans to remotely disable the colony's shields.
The USS Enterprise (NCC-1701-C) responded to the colony's distress calls and engaged the attackers, but was destroyed in the battle. The Romulan attack continued, and the colony was destroyed.
Only two survivors were found among the ruins by subsequent Federation vessels responding to the colony's distress call, one of them an infant Worf.
The Klingons regarded the Federation response as an honorable act, and Federation relations with the Klingon Empire improved in the aftermath, setting the stage for the Klingon-Federation alliance.
Twenty years later, an additional group of survivors was found to have been held prisoner by the Romulans. At this point, Khitomer was considered to be within Romulan territory.