In the 24th Century, a renegade band of freedom fighters known as the Maquis are operating outside Federation law. When one of its ships disappears in 'The Badlands' with undercover Starfleet Security Officer Tuvok aboard, the Vulcan's new starship, the U.S.S. Voyager and his Captain, Kathryn Janeway, are dispatched to retrieve him. Captain Janeway recruits a Starfleet washout and Maquis prisoner, Tom Paris, to help on the mission. Before Voyager departs Deep Space 9, Paris rescues a fresh Academy graduate, the starship's Ops Officer Harry Kim, from some of Quark's salesmanship. The two of them become friends, even with warnings to Kim that Paris caused the death of fellow crewmembers and then lied to cover it up. Shortly after Janeway leaves last-minute instructions about her pregnant dog with her fiance Mark, her ship encounters a bizarre phenomenon in 'The Badlands' that sweeps it some 70,000 light years away to the Delta Quadrant.
The Caretaker has been providing for the native Ocampa people and their world since his race severely damaged their atmosphere in an accident. Knowing his own death nears, the aged alien is collecting people of different origins to test them for compatible DNA to provide a mate that will bear offspring to carry on his work. The Caretaker kidnaps both crews and examines them, but they are returned some three days later, except for Kim from Voyager and B'Elanna Torres, a half-Klingon, half-human Engineer from the Maquis vessel. Banding together to successfully rescue their missing mates, the two crews encounter Neelix, a Talaxian scavenger and jack-of-all-trades and his lover Kes, an Ocampan who strives for more than her people's sedate and dependent lifestyle underground.
As the crew tries to adjust to the merging of Starfleet and Maquis personnel, the differences are apparent. One heated procedural discussion in Engineering ends with Lieutenant Carey in Sickbay with a broken nose thanks to B'Elanna, who later gets a little advice from Chakotay on getting along and controlling her temper. While Janeway looks to fill the many still-vacant jobs on board, Neelix and Kes volunteer to serve -- he as a cook and guide, and she as a gardener of airponic vegetables to save replicator power. Voyager must make do with its Emergency Medical Hologram Doctor, with Tom Paris to assist him. Chakotay recommends B'Elanna as Chief Engineer and Janeway agrees to consider it.
Exploring a planet which has very recently been rendered uninhabitable by a global disaster, Janeway and Paris are separated from the rest of their away team and somehow find themselves in the same place, but hours before the cataclysm that consumed the planet's entire civilization. Their attempts to remain anonymous while trying to find a way back to their own present land them in the middle of a protest against a polaric energy plant, which may be the cause of the world's destruction. At first, Janeway is adamant that the Prime Directive be adhered to, but when she discovers the possibility that her presence may have caused the disaster in the first place, the captain decides to set aside Starfleet's first rule.
Searching for deposits of refinable dilithium, Voyager stops off at a moon, where Chakotay, Kim and Neelix beam to the surface. It turns out that this moon is not uninhabited. A group of aliens there seem to have left a dilithium trail, and one of them attacks Neelix. When the others come to his aid, Neelix's lungs have been removed, and only some innovative but risky gambles taken by Voyager's holographic doctor can keep him barely alive. The aliens flee the moon in their own ship, and Janeway orders a pursuit. It turns out that the attackers are simply trying to survive themselves, their species all but wiped out by a deadly disease. Their only hope for survival is to take working organs from others - and they cannot return to lungs to Neelix, for they have already been used.
On a morning walk around the ship, Janeway ponders loosening the traditional protocols of command amid Voyager's unique aloneness. Her visit to Engineering convinces B'Elanna her department is under inspection. When Janeway enters the Mess Hall, Kim and Paris debate the propriety of inviting their Commanding Officer to join them. On the Bridge she confides to Chakotay her yearn for a Counselor, believing the crew may be homesick, but he describes his people's use of an animal spirit guide and offers to help her discover her own guide. Then sensors detect a nebula emitting a high level of useful omicron particles, and the Captain decides to collect some and do a bit of exploring. Back in the Mess Hall, Neelix can't believe Janeway entered the nebula, but Kes speaks up for the romance of exploration until they turn to see globules spattering and attaching themselves to the ship's hull. The globules lead Janeway to order the exit of the nebula, but that takes some doing.
Harry's sensor sweeps for space anomalies detect a wormhole which Janeway diverts Voyager off course to investigate. Though a probe is able to determine that the wormhole leads homeward to the Alpha Quadrant, the wormhole is too small to travel through. When the probe is scanned by a ship on the other side, the crew begin using it as a relay satellite and make contact with a Romulan ship. Though the Romulan captain is skeptical of Janeway's claim that Voyager is in the Delta Quadrant, he eventually realizes the truth and offers to help transmit messages home. Later, B'elanna discovers a possible way to beam through the wormhole to the Romulan ship, but this method of returning to the Alpha Quadrant is halted by an unforseeable problem.
Kim returns alone in a shuttle from a trip to Benea which he made with Tom Paris. After getting entangled with a scientist's wife, and by all accounts murdering the scientist in question, Paris has been sentenced to relive the crime from the victim's point of view every 14 hours. Janeway, despite Tom's admittedly less-than-exemplary record, needs to know for herself if Tom is guilty of the crime. When it turns out that the Benean punishment is reacting badly to Tom's human physiology, he is taken back to Voyager. Mysteries begin to pile up - why are the neighboring warlike Numiri attacking Voyager? And who really committed to murder? The answers can only come from one source - Tuvok must mind-meld with Paris to experience the forced reenactment of the incident himself.
Investigating the possibility of a new element detected in the rocky bodies comprising a planet's ring system, an away team beams down to one of the asteroids and finds the ground littered with dead bodies encased in a residual shell. As the away team conducts a visual survey - at Chakotay's request to avoid desecrating the ritually-disposed-of deceased - a subspace phenomenon occurs, prompting an emergency beam-out. But when the away team transports back to Voyager, Kim doesn't return, his place taken by a newly-arrived body. Harry finds himself among a race of ritualistic people who believe he has returned from their afterlife, and is constantly besieged with questions about 'the next emanation'. An alien named Patera, in the meantime, is revived about Voyager. She finds herself losing faith in the possibility of the next life, while Harry is the subject of intense curiosity and study by Patera's people.
Voyager is intercepted by a ship from Sakarris, an planet with an advanced culture renowned for its hospitality; Sakarran magistrate Gath offers an extended visit to his planet, which Janeway accepts. During this visit, Harry finds out that the Sakarrans have developed transportation technology that could send Voyager at least halfway home, if not all the way. But the Sakarrans have their own rule - much like Starfleet's Prime Directive - that will not permit them to share this technology with less advanced cultures. However, a faction on Sakarris is willing to exchange a sample of their trajector with Voyager's crew in exchange for something only the outsiders can offer. Janeway will not conduct an unofficial or illegal exchange, but she finds out that there are those among her crew who will.
A visit to the surface of a habitable planet becomes less than routine when a Kazon ship is detected nearby. All away teams are recalled to Voyager, but Seska can't be found. Chakotay finds her in a cave nearby, where the two of them are attacked by Kazons but escape. The Kazon ship is sending a distress signal, and despite her own misgivings and Neelix's warnings, Janeway sends an away team to the ship. It is discovered that the Kazons somehow acquired some Federation technology and suffered a fatal accident while trying to install it on their ship. Other Kazon ships are on the way, and Janeway faces the possibility that someone aboard Voyager has decided to ally themselves with the enemy.
As Voyager passes near a protostar, Janeway and Torres try to beam some samples of its photonic material aboard. When they try to enlist Harry's help in studying it, they find that he has disappeared from the ship. Chakotay and Tuvok go to where Harry was last found - the holodeck - and try to learn what happened to their comrade by interacting with Harry's Beowulf holodeck program. Even Chakotay and Tuvok vanish when Grendel comes to ravage the Hall Heorot. Someone needs to venture into the holodeck to find where the missing crewmen are going, or if they're still alive. Into Hrothgar's keep steps a new warrior, the only member of Voyager's crew immune to the threat of being snatched out of the holodeck, but can the holographic doctor grapple with something other than a medical emergency?
A shuttle has returned badly damaged and of its passengers, Tuvok has minor injuries but Chakotay is diagnosed as brain dead. Logs show that during an encounter with a black nebula, all of Chakotay's neural energy was depleted and would cause his death if not replenished quickly. Several inexplicable events begin unfolding after B'Elanna places Chakotay's medicine wheel above him: Paris locks helm control out and changes course twice, while B'Elanna shuts down the warp core. Kes announces she can sense an alien presence that may be possessing the officers, and because they deduce that the alien can control different people at different times, Janeway has to transfer all command codes to the Doctor - but even he is soon found deactivated.
Janeway grows concerned when B'Elanna, Paris, and Lieutenant Peter Durst fail to report in for beam-up after an away mission. In reality, the phage-plagued Vidiians are kidnapping visitors and masking the landscape to cover their operation on the planet. The scientist Sulan is in search of a cure for the deadly disease of his people. During an experiment, B'Elanna is literally split into two separate beings -- one fully Klingon, the other fully human -- by Sulan, who believes Klingons may be immune to the phage. Since the Vidiians are too weak to do their own labor, the unused hostages including Paris, Durst and another Talaxian are put to work digging tunnels.
An alien ship contacts Voyager and asks for Neelix by name; when the party seeking Neelix turns out to be a Haakonian named Jetrel, Neelix reacts badly. Jetrel was a scientist who developed the metreon cascade, an immensely powerful weapon that destroyed 300,000 Talaxians - including Neelix's family - during a war with the Haakonians fifteen years ago. Jetrel announces that Neelix could be suffering from a terminal condition resulting from minimal exposure to the metreon cascade, and offers to try to study him to find a cure. But Neelix wants no part of easing Jetrel's conscience.
After a Maquis officer named Dalby breaks with procedure and replaces a faulty bioneural circuit without reporting the malfunction, Janeway assigns Tuvok - himself a former instructor at Starfleet Academy - to bring Dalby and a handful of other problematic Maquis up to speed on Starfleet protocol. This task proves more daunting than Tuvok could have imagined, since even the most worrisome Academy cadets at least wanted to be in Starfleet. Despite an order from Chakotay to learn the Starfleet ropes, Dalby and his fellow trainees are determined not to learn a thing - until their lives depend on it.