Cardassian history tends to consist of extremes; once a peaceful and spiritual people, their planets poor resources proved unable to support their expanding population and starvation and disease became rampant. Millions of deaths resulted, leading to a general breakdown in the government. The military forces of the planet staged a takeover and launched several wars against their neighbours in order to secure new resources. Although further millions where lost in these wars, the military government did succeed in stabilising the situation on Cardassia.

In 2346 the Cardassians invaded Setlik III, believing it to be a base to be used in an invasion of their own territory by the Federation. A prolonged period of tension punctuated by hostilities resulted. In 2355 the Federation dispatched a Constellation class starship in an attempt to make peace, but the Cardassians rejected the offer and forced the ship to flee. Hostilities officially ended in 2367, although the Cardassians remained less than friendly.

In 2372 a civilian uprising deposed the military government. Suspecting Dominion involvement in the coup, the Klingons launched an invasion of Cardassia; the Federation opposed this action and was successful in forcing the Klingons to halt their advance into Cardassia, although this destroyed the Federation-Klingon alliance and resulted in a short period of hostilities between those two powers. The Federation shipped considerable aid to the devastated Cardassian government.

Humiliated by having to rely on charity from a former enemy after a relatively quick and easy defeat at the hands of the Klingons, Gul Dukat led a Dominion takeover of Cardassia and was installed as ruler of the region in 2373. Cardassian forces have subsequently fought alongside the Jem'Hadar in the Dominion War.