The last season of Star Trek: Deep Space Nine began with Sisko having a vision, while on Earth. He saw a woman buried in the sand on the desert planet Tyree, and immediately sketched the woman's face, as not to forget her. Jake, who had come with his father to his grandfather's restaurant on Earth, said that he recognized the woman from one of his grandfather's photos. Sisko's father, Joseph, told him that the woman's name was Sarah, and she was really his mother, but had left for Australia and died while he was very young. Joseph gave Sisko a locket that had belonged to Sarah, and he noticed that it had the inscription "The Orb of the Emissary" written in Ancient Bajoran on it. Meanwhile on DS9, Major Kira had been promoted to Colonel, and had taken the role of Acting Commander. Romulan Senator Cretak had requested permission to set up a Romulan hospital on one of the Bajoran moons, and Kira agreed. Later she found that the Romulans had been storing weapons there. She demanded that the be weapons removed, or she would do it herself, possibly ending the alliance between the Federation and the Romulan Empire. Back on Earth, Captain Sisko, Jake, and Joseph were about to leave for Tyree to discover the answer to Sisko's vision, when Ezri Dax came in the door, saying she was the new host to the Dax symbiont. Ezri explained how she was the only Trill on a Federation ship while the injured Dax symbiont, taken from Jadzia, was being returned to the Trill home world. The ship wouldn't make it in time to save the symbiont, so Ezri had to be joined with it in order to save it. She joined the Sisko generations on their trip to Tyree. Meanwhile, Colonel Kira was blockading Romulan ships from the Romulan hospital on the Bajoran moon. Not wanting to risk a war with the Dominion, as well as the Federation-Klingon Alliance, the Romulans backed down. The Siskos and Ezri arrived at Tyree, and were guided by Sisko's visions on a long trek through the desert. Eventually they reached a spot where Sisko began madly digging. He uncovered an orb--the Orb of the Emissary--and when he opened it, the orbs lit up and the wormhole suddenly reopened, throwing the Pah-Wraiths out, who had somehow taken over temporarily. Sisko received a vision from a particular Prophet--it was his mother, Sarah. She said that she had possessed Sisko's mother so he would be born, and "the Sisko" could fulfill his destiny as Emissary. Joseph was returned to Earth, and Jake, Captain Sisko, and Ezri Dax, returned to Deep Space Nine.
Colonel Kira is kidnapped by a Bajoran who takes her to the abandonned Cardassian space station, Empok Nor. There she met Dukat, who was leading a Bajoran Pah-Wraith cult--people who saw the Pah-Wraiths as the true Prophets. While Kira was there, one of the Bajoran women went into labour, and the child was found to be half Bajoran and half Cardassian. Dukat told the cult that it was a symbol of the bond between himself and the Bajoran people sent by the Pah-Wraiths, but Kira knew that he had really fathered the child. To escape from being found out, Dukat told the cult that the Pah-Wraiths wanted the people to join them by committing suicide. Kira revealed him as a fraud by proving that he had no intention of killing himself with the others. Dukat fled, and Kira was saved by the Defiant.
Worf, after a fight with the Dominion on a Klingon ship, was declared missing in action, and Captain Sisko was forced to call off the search due to strategic concerns. Ezri stole a runabout, and went to find him herself, and she did. However, on their way back to DS9 they were caught in a fight with the Jem'Hadar, and forced to beam down to a planet's surface for safety. In the haste, they forgot to bring communications equipment with them, and were unable to contact the station. They were taken prisoner by the Breen and put in a cell on a Breen ship which was heading to an unknown location at maximum warp.
Kai Winn arrived on Deep Space Nine and received her first vision from the Prophets, who told her that she would be provided with a guide, who with she would lead Bajor's restoration. Dukat appeared on the station, surgically altered to look like a Bajoran, and claimed that he was Winn's guide.
On a Jem'Hadar ship, the Female Changeling told Weyoun about a disease which had infected the Great Link and was killing all the Changelings, when the Breen ship, which Ezri and Worf were being held prisoner on, met up with their ship. Weyoun made the announcement that the Breen was allying with the Dominion.
Kai Winn, not knowing that her guide was really Dukat, pledged with him to do whatever the Prophets requested of them to restore Bajor, even if the Emissary stood in their way. However, later when her guide asked her to worship the Pah-Wraiths as the true Prophets, the Kai was outraged.
Damar refused to sign the treaty which would officially bring the Breen into the Dominion because the Female Changeling had promised the Breen rights to Cardassian territory after the war. Feeling betrayed by the Dominion, Damar helped Ezri and Worf escape execution and gave them a message for the Federation saying they had an ally on Cardassia Prime–himself.
Kai Winn realized that the vision she had received was really from the Pah-Wraiths, and beginning to believe that they really were the true Prophets, she sided with her "guide". Upon returning to Bajor, Kai Winn obtained the ancient Kosst Amojan texts, which would tell her how to release the Pah-Wraiths into the Celestial Temple. The book was empty, and Winn thought she must determine how to reveal the words it contained.
After the Breen attacked and destroyed Starfleet Headquarters on Earth, the Dominion and the Breen took another step by reclaiming the Chin'toka System--the Federation's only foothold in Cardassian space. In the space battle that ensued, something about the Klingon ships made them immune, but the Federation and Romulan vessels were vulnerable to a powerful Breen energy-dampening weapon. Many ships were lost, including the Defiant, and the Federation lost the Chin'toka system.
Later, Dukat was questioned by Winn's personal assistant, whom he revealed his true identity to as a threat. The assistant made the Kai aware of who her "guide" really was, and enraged with anger, she stabbed her assistant, killing him. When blood from the knife dripped onto the Kosst Amojan, the words appeared in a blaze of fire. She discovered that she must release the Pah-Wraiths from the Fire Caves on Bajor by reading certain passages from the book while in the caves.
As Damar's resistance against the Dominion gained momentum and more and more Cardassians joined his cause, Sisko ordered Colonel Kira to go to Cardassia Prime and aid Damar in resistance tactics. Next, Klingon Chancellor Gowron came to the station and awarded General Martok with the Klingon Order of Kahless, after which he took over as leader of the Klingon effort in the war. He foolishly began to order Klingon ships into ridiculous battles in which they were severely outnumbered.
Doctor Bashir had discovered that Odo was also infected with the disease killing the Changelings. Once he was unable to obtain Odo's Starfleet Medical records, he realized that Odo must have been infected by Secton 31--an above top secret level of Starfleet, which wasn't officially listed--as a carrier to infect the Founders. Doctor Bashir and Chief O'Brien lured Sloan, a Section 31 operative, to Deep Space Nine in order to find a cure for Odo. Knowing that Sloan wouldn't just give them the answer, Bashir tried to use a Romulan mind probe to extract the information from him. However, Sloan activated a neuro-polarizing device in his brain to commit suicide. Acting quick, Bashir was able to stop Sloan's death, and he and Chief O'Brien used a device which allowed their minds to link with Sloan's to go into his mind and get the information themselves. They succeeded, and Odo was cured.
Garak joined Kira and Damar in the Dominion resistance, and they were forced into hiding by a Jem'Hadar ambush. They managed to sneak out to bomb a Jem'Hadar barrack, and more Cardassians became aware of and joined Damar's resistance. After many Cardassian uprisings, Weyoun announced that for every act of terrorism against the Dominion, one Cardassian city would be annihilated. Damar, Kira, Garak, and a band of Cardassians managed to invade Dominion Headquarters on Cardassia Prime. Damar and the last Weyoun clone were killed in the battle.
The Dominion made the strategic move of retreating to hold the Cardassian territory they had gained, and the Federation-Klingon-Romulan Alliance prepared to force the Dominion and Breen off of Cardassia Prime. The great space battle for Cardassia Prime began as armada after armada of Federation, Klingon, and Romulan ships led by the new Defiant II battled the Dominion, Breen, and Cardassian ships around the planet. Suddenly, the Cardassian ships switched sides, and began firing on the Dominion and Breen ships. Enraged by betrayal, the Female Changeling declared that the Dominion would exterminate the entire Cardassian race--but it wouldn't be so. Odo transported from the Defiant II to Dominion Headquarters on Cardassia Prime, linked with the Female Changeling to gain her trust by healing her, and in the process, convinced her to call a cease fire. On Deep Space Nine she signed the documents, officially declaring the Dominion's surrender.
In the Fire Caves on Bajor, Kai Winn had killed Dukat as a sacrifice to the Pah-Wraiths. Sisko, led by a vision from the Sarah Prophet, went to the caves himself, only to see Dukat be revived by a Pah-Wraith, and Kai Winn spontaneously combust! Sisko battled Dukat until they both fell into the flames. Sisko received a vision from the Sarah Prophet saying that the Pah-Wraiths had been sealed back where they belong, and Dukat was with them. She said that Sisko would stay in non-corporeal form with the Prophets to learn from them, and return from the Celestial Temple at an unprecedented time. Captain Sisko had fulfilled his destiny.
On Deep Space Nine, Chief O'Brien had gone to Earth to teach engineering at Starfleet Academy, Worf had become the official Federation Ambassador to Q'ronoS, and Odo had returned to heal and teach his people to trust the Solids.