Having returned to Earth a couple of months ago, Sisko waits for the Prophets to instruct him on what to do next. When he receives one, he begins searching for the woman behind the face in the sand in his vision. Meanwhile, back on DS9, Kira deals with a promotion and handling the decisions surrounding her command, and finding herself wishing for the return of Sisko. And Worf deals with the loss of his wife, Jadzia Dax.
Ezri Dax joins Sisko and his family on his quest for the Orb of the Emissary. Colonel Kira mounts a blockade around a Bajoran moon, where the Romulan hospital is - along with thousands of Romulan missles (claimed to be defensive in purpose). Quark joins Bashir & O'Brien as they join Worf, aboard a Klingon warship as they mount a dangerous mission in Jadzia Dax's name in an effort to get her spirit into Sto-vo-kor, the Klingon's heaven.
Sisko tries to convince Ezri to stay in Starfleet and serve aboard DS9, as Ezri tries to get to know Jadzia's friends aboard the station, especially Worf. Meanwhile, Garak tries to deal with a severe bout of claustrophobia.
When a programming glitch won't go away, mobsters take over Vic's and open for business, but the DS9 gang takes it personal when their favorite hangout is no longer their favorite, and they plan to get the new management ousted.
While making plans to attend a medical conference on the Romulan home world, Dr. Bashir is contacted by Sloane of Section 31 and recruited to determine the health of a high-ranking Romulan official. Things turn more desperate, though, when the ranking Starfleet admiral traveling with him, who knows about Section 31's interest in the conference mysteriously suffers a brain aneurysm after Dr. Bashir finds out that Sloane is traveling with the group, as well.
The Prophets have told Sisko they do not approve of his impending marriage. Having been captured by the Breen, Ezri and Worf still don't know why the Breen would even bother to capture them. Some Cardassians are beginning to think their alliance with the Dominion was a grave mistake. Gul Dukat, disguised as a Bajoran, sets foot on DS9, and continues to unfurl his plan.
Kai Winn gets unknowingly involved with Gul Dukat, surgically altered to resemble a Bajoran, using the name 'Anjohl.' Tensions further escalate between Weyoun and Legate Damar, as the Dominion gather to sign a peace treaty with the Breen, which includes granting the Breen certain Cardassian territories. Having been held captive by the Dominion, Ezri and Worf try to escape from the Cardassian home world.
After the Breen attack Earth, mixed emotions abound on DS9. Kai Winn reveals her true feelings regarding the Prophets to her spiritual guide, a Bajoran farmer named Anjohl, who is a surgically altered Dukat, and turns her back on them, and convinced by him to embrace the Pah Wraiths. On the home world of Cardassia, Legate Damar mounts a resistance to the Dominion.
Kira gets sent behind Cardassian lines in an effort to train them in resistance fighting. When Dr. Bashir learns of the deadly disease Odo is infected with, he gets met with resistamce whilst trying to obtain his medical records from Starfleet. Martok gets blindsided by Gowron when he arrives on DS9, announcing he has assumed command of the Klingon fleet.
Odo is affected by the disease threatening to eliminate his race more than he lets on, while Kira has to deal with the Cardassians' dislike of her. Even though General Martok sees Chancellor Gowron's move as part of a political vendetta, he does nothing about it. Worf suspects Gowron's military strategies are meant to humiliate Martok's command abilities, without thought the consequences have for Klingons as a whole. Meanwhile, O'Brien suggests to Bashir he announce he's found a cure to the Changelings' disease to lure someone from Section 31 to DS9.
Odo begins recovery from the deadly disease which Dr. Bashir tells him had been engineered by Section 31 in order to wipe out the Founders' entire race, A resistance mission goes bad for Kira and Garak, and they end up hiding in the basement of the house which Garak grew up in. They soon hear Legate Damar - who had been on their mission and was hiding with them - has just become a casualty of war. The Grand Nagus has chosen Quark to become his successor, upon his impending retirement on the pleasure planet, Risa.
As the Dominion War comes to an end, Dukat goes to the Pah Wraiths to awaken them. Meanwhile the Dominion turn on the rebelling Cardassians, destroying them city by city. Will the Alliance prevail over the Dominion? Will Garak and the Rebellion stop them before the destruction of Cardassia? Will Sisko stop the Pah Wraiths from rising?