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 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 alliance has deposited an ammunitions dump, claiming it in the name of defense for a Romulan hospital. And Quark joins the rest of the DS9 crew 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 Stovokohr, the Klingon equivalent of 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 that they do not agree with his impending marriage. Ezri and Worf are captured by Dominion forces. Some of the Cardassians are beginning to regret their alliance with the Dominion, as Gul Dukat, disguised as a Bajoran, sets foot on DS9.
Kai Winn gets unknowingly involved with Gul Dukat, disguised as a Bajoran. Tensions further escalate between Weyoun and Gul Damar as the Dominion gather to sign a peace treaty with the Breen, including certain concessions of unknown territories by the Cardassians, as Ezri and Worf try to escape the Cardassian home world.
After the Breen attack Earth, mixed emotions abound on DS9. Having revealed her secret regarding the Prophets to Dukat, Kai Winn turns her back on them, only to be convinced by Dukat to embrace the Pah Wraiths. And 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 that Odo is infected with, he gets met with barriers when trying to obtain his medical records from Starfleet. And Martok gets blindsided by Gowron when he arrives on DS9, announcing that he has assumed command of the Klingon fleet.
Odo is affected by the disease threatening to eliminate his race more than he lets on to, while Kira has to deal with the Cardassian's dislike of her. Even though General Martok sees Chancellor Gowron's move as part of a political vendetta, he does nothing about it.
Odo begins recovery from the deadly disease as Dr. Bashir informs him of Section 31's intentions of wiping out his race. A resistance mission goes bad for Kira and Garak and they end up hiding in the basement of the house that Garak grew up in, as they learned that Gul Damar becomes a casualty of war, who is also hiding with them. And the Grand Nagus chooses Quark as his successor upon his impending retirement to Reysa.
Sisko leads, what he hopes will be, a final all-out assault on Cardassia Prime, as Kira and Garak mount a suicide assault on the Cardassian headquarters, occupied by the Dominion, who kill innocent women and children village by village in retaliation for Resistance attacks.