The Federation-Tzenkethi border was the division between the United Federation of Planets and the Tzenkethi. The Federation had several colonies near it in the early 2370s, such as Barisa Prime. The Helaspont Nebula was located in the same sector as Barisa Prime. A Tzenkethi settlement near the border was on M'kemas III.

In late 2371, a Founder took control of the USS Defiant and had the starship cross the border into Tzenkethi space. (TNG: "Face of the Enemy"; DS9: "The Adversary")