On the edge of Borg territory, which consists of thousands of systems, the crew discovers a narrow passage devoid of Borg activity. Dubbed the "Northwest Passage," it is filled with gravimetric distortions, but as Tom Paris puts it, "Better to ride the rapids than face the Hive." While the Northwest Passage appears safe, Janeway tells the crew that a confrontation with the Borg may be inevitable and instructs them to prepare for one. While Kes and The Doctor work on an antibody to combat the Borg assimilation nanoprobes, the Ocampan has a vision of dozens of Borg corpses.
Kes' premonition is followed by several more concerning the death of Borg and Voyager's destruction. Before Janeway can react, however, Harry Kim announces that fifteen Borg cubes are headed their way. The crew prepare for a fight, but the cubes ominously pass them by, as if they were not heading toward Voyager, but fleeing from something. As Janeway and Chakotay discuss the possibility that Voyager will be forced to remain in the Delta Quadrant, Tuvok informs them that the Borg ships' power signatures have stopped and the armada is dead in space. They follow the cubes' path only to discover that all of the cubes have been destroyed.
There is an alien bioship attached to the hull of one of the remaining cubes. Chakotay, Tuvok, and Kim beam aboard the cube to investigate, where they see the same image Kes described: dozens of Borg corpses piled on top of one another. They see no aliens but can hear roars coming from elsewhere within the cube. As they scan the bioship, Kes has a vision of Harry screaming in pain. B'Elanna Torres beams the away team back with the never before tried "skeletal lock" (locking onto the minerals in the away teams' bones) but not before the alien returns and injures Harry just as Kes predicted. The bioship detaches itself from the Borg cube and fires at Voyager but does not pursue it. Kes can hear the telepathic alien say, "The weak will perish."
Despite the new threat, Janeway decides Voyager must maintain its original course as the Northwest Passage is only a day away. The Doctor discovers along the way that an infection caused by cells from the alien is consuming Harry's body. He is unable to combat the infection with traditional medicine but thinks he can modify Borg nanoprobes to destroy the alien cells; however, it may be too late for Harry. Meanwhile, Tuvok and B'Elanna discover that the Borg call the alien Species 8472 and have been defeated by it several times. Upon reaching the Northwest Passage, Voyager is greeted by 133 bioships.
As before, Kes is able to hear the aliens say, "The weak will perish." They are arriving through some kind of quantum singularity (explaining the gravimetric distortions) and intend to destroy everything. Janeway considers the possibilities and comes up with a radical idea: an alliance with the Borg. Her plan is to offer The Doctor's cure to the Borg but withhold it until the Borg escort Voyager through their space. The crew does not question Janeway's judgment, but once the rest are gone, Chakotay admits he thinks what the captain is proposing is too great a risk.
Voyager travels to the nearest Borg star system, where a cube announces that it will assimilate the ship and places a tractor beam on it. Janeway explains the situation and the cube beams her aboard it. She and the Collective's voice are close to coming to an agreement when a quantum singularity emerges and ten bioships emerge. Ignoring several Borg cubes, the bioships head straight for a nearby planet. They emit a massive energy burst that obliterates the entire planet, and the cube, with Voyager in tow, narrowly escapes the resulting explosion.