Per Bajoran custom, her family name, Kira, precedes her given name, Nerys. She has two brothers (Kira Reon and Kira Pohl), and her parents' names are Kira Taban (played by Thomas Kopache throughout the series) and Kira Meru (played by Leslie Hope in "Wrongs Darker than Death or Night").

The backstory of the character states that Kira Nerys was born 2343, in Dakhur province, Bajor, during the 50-year Cardassian occupation of the planet. She was raised in a labor camp. Her family were members of the artisan caste, namely sculptors of clay, or potters. At age 12, Kira was recruited into the Shakaar resistance cell, part of an underground movement which carried out guerrilla attacks against Cardassian military and civilians with the ultimate goal of ending the occupation.

Kira is assigned as the senior Bajoran Militia officer aboard Deep Space Nine, acting as the station's executive officer under the Starfleet commander Benjamin Sisko who posted to command the facility. In the early episodes of the series after Cardassia withdrew from Bajor, the recently ranked Major Kira, now at age 26, became an influential figure in Bajor's reconstruction and the politics of the region, due to her assignment to Deep Space Nine, and her closeness to Benjamin Sisko, whom the Bajorans believed to be an emissary from the Bajoran Prophets.

Initially, Kira was opposed to the Federation presence on DS9, feeling that the Bajoran people should have nothing to do with the Federation as Bajor had just endured a 50-year occupation by the Cardassians. Over time, her sentiments changed and she became one of the strongest supporters of Bajor joining the Federation and an essential ally to Benjamin Sisko. This conversely contrasted to her increasingly nuanced religious faith that came from dealing with the Bajoran religious leader, Winn Adami, for whom Kira held increasing contempt for her shamelessly treacherous opportunism and arrogance.

Though she is a member of the Bajoran Militia, Kira is an invaluable help to Starfleet, often commanding Starfleet personnel directly through her authority as DS9's executive officer. Indeed, during the first year of the Defiant's commission at the station, she also serves as the ship's first officer, a situation that only alters upon the arrival of Lt. Commander Worf, who assumes the role as the next most senior Starfleet officer of command grade. When the Dominion recaptures Deep Space Nine at the start of the Dominion War, Kira remains aboard the station as liaison officer, as part of Bajor's non-aggression pact with the Dominion. Her role allows her to organize a resistance cell, including Rom, Quark and Jake Sisko. They smuggle intelligence to Starfleet which indicates that the Dominion has begun to dismantle the minefield preventing Dominion reinforcements arriving from the Gamma Quadrant. She also manages to sabotage the weapons systems, which then allows Starfleet to retake Deep Space Nine.

Kira's experience in the Bajoran Resistance earned her a promotion to a rank equivalent to lieutenant colonel. This is equivalent to a Starfleet field commission of commander, a fact taken advantage of by Starfleet to more easily assist the Cardassian Resistance wage a war of independence against the Dominion. To provide that assistance, Kira, Odo and Garak get smuggled into Cardassia to teach Damar the tactics of organizing a resistance movement with a decentralized command. Their resistance cell manages to infiltrate a Dominion shipyard and steal the Breen weapon against which Federation ships were defenseless. Their actions allowed Starfleet engineers to develop shields that could counter the weapon. At the conclusion of the war (and the end of the series), Kira takes command of DS9 after the disappearance of Sisko.