Intent on stopping Archer and Enterprise's mission, the diabolical Suliban take the crew hostage when it is discovered that Archer has mysteriously disappeared off the ship. While stuck in the decimated remains of the 31st century, Archer and Daniels work to find a way to get back to Enterprise; and Daniels worries that the future existence of The Federation may be in jeopardy as a result of his impulsive action to remove Archer from Enterprise, forever changing the course of history.
T'Pol tells Archer and Trip a story about her great-grandmother T'Mir and three other Vulcans who made first contact with humans after crash landing in a small Pennsylvania town in the 1950s. T'Pol's story shocks Archer and Trip because her account is much earlier and very different from what history books reported.
After unwittingly wandering into a minefield in Romulan territory, Enterprise becomes trapped when struck by an undetonated mine. When Reed takes a space walk to try to defuse the mine, he inadvertently gets pinned to the outer hull and Archer must chose between saving Reed or abiding by the Romulans orders to depart the airspace immediately.
Enterprise, in desperate need of extensive repairs, docks with a mysterious, high-tech, automated space station that inexplicably and amazingly fixes everything, making it almost too good to be true. While waiting for the repairs to be completed, the Enterprise crew searches the unmanned space station and discovers its unique and horrifying power source.
Archer spends a fretful night in Sickbay with Dr. Phlox after Porthos, Archer's pet beagle, picks up a deadly virus on an alien planet. Meanwhile, crew members believe Archer's increased stress level is due to Porthos' illness, but Dr. Phlox suspects it has to do with Archer's repressed sexual tension and urges Archer to discuss it with T'Pol.
When Enterprise is in need of fuel, Archer discovers a desolate mining colony that is being controlled by Klingon marauders who are bullying the colonists and hoarding their fuel. After Archer discovers the problem, the crew trains the colonists to defend themselves and prepare for a final showdown against their Klingon oppressors.
T'Pol brings Archer with her on a top-secret mission when she is dispatched by the Vulcan High Command to capture a fugitive that has eluded their authorities for nearly two decades. Meanwhile, T'Pol reveals to Archer a dark and violent secret that she repressed, and Trip, who fills in for Archer while he is away, finds the weight of being the Captain hard to bear.
Reed accidentally leaves his communicator on a pre-warp alien planet during a visit, and when he returns with Archer to retrieve the crucial technology, they are captured by soldiers who accuse them of being enemy spies. Meanwhile, Trip and Mayweather use the cloaking technology of the damaged Suliban Cell-Ship they had previously captured in an attempt to rescue Archer and Reed before they are executed.
On a "typical" day on Enterprise, the crew finds their routine tasks turn into uncharacteristically strange obsessions over trivial matters. The crew's increasingly erratic and often humorous behavior includes: Archer's preoccupation with writing the preface of a biography about his dad; Trip's fixation on adjusting the Captain's chair to perfection; Hoshi's obsession with her cooking; and Reed's concern with a Tactical Alert.
Following her first experience in the transporter, a series of eerie events leads Hoshi to question whether she is the same person. Feeling fearful and helpless, Hoshi becomes unsure of herself wondering if she is losing her mind, or if the transporter has somehow changed her, or if there is an alien threat behind all of these bizarre happenings suddenly taking place.
Trip Tucker boards an alien cargo vessel to help repair a stasis pod holding a beautiful woman in suspended animation. When the woman accidentally awakes, she reveals she's not a passenger, but a prisoner.
When a lethal neutronic storm approaches faster than Enterprise can escape, the entire crew takes shelter in the most heavily shielded part of the ship - the maintenance shafts inside the warp nacelles - for several days. They also provide refuge to a group of aliens who aren't entirely upfront about themselves.
Trip Tucker is alone on a test mission aboard Shuttlepod One when he is fired upon by a territorial alien and forced to land on the night side of a moon. As he tries in vain to contact Enterprise, he discovers his alien foe has also made an emergency landing nearby, and the two nemeses must contend with each other as the extremely hot rising sun threatens their survival.
While Enterprise visits a planet where an Interspecies Medical Exchange conference is taking place, Dr. Phlox tries to obtain research on a terminal disease from the Vulcan contingency there. But he must not reveal that T'Pol has contracted this disease, because that knowledge would forever stigmatize her among her people.
A military conflict erupts between the Vulcans and Andorians over a small terraformed planet that both sides make claim to. In the midst of the skirmish, the Vulcans announce they wish to discuss terms for a cease-fire, but Imperial Guard officer Shran believes the only one he can trust to mediate such a negotiation is Jonathan Archer, so the captain and his ship are called into the fray.
Far beyond where any Earth vessel has ventured before, the Enterprise crew is shocked to find a small craft adrift in space that contains what appears to be a human corpse. Trip Tucker and Malcolm Reed discover the craft holds some strange secrets, and the mystery deepens when the Suliban arrive making claim to the salvage. On top of that, Captain Archer is confronted by the Tholians, who also aggressively try to procure the enigmatic vessel.
Upon leaving the Enolian homeworld in a shuttlepod, Archer and Tucker are mistakenly arrested and placed on a prisoner transport vessel bound for the penal colony Canamar. Before the error can be rectified, one of the alien inmates engineers a takeover of the transport, leading Archer to engage in a dangerous gambit.
When Enterprise is enveloped by a vast alien vessel filled with a species that appear only as wisps of vapor, these non-corporeal alien beings capture Enterprise and take form by invading various crew members' bodies to learn more about the humans, or so they say. In an attempt to get back control of Enterprise and to have his crew members' lost souls returned to their appropriate bodies, Archer enlists T'Pol's powers of mind control to determine what the aliens really want.
Archer stands trial before the Klingon Tribunal who have charged him with firing on a Klingon warship and providing aid to refugees on the run from the Klingon empire for which the punishment is death. When the prosecution paints a skewed and violent picture of the events in question, Archer challenges his appointed Klingon legal counsel to buck their cruel justice system and let him present his side of the story in the hopes that he will prevail. In the process, Archer learns that Klingons haven't always been a warrior society and that there are Klingons who want to lead a more peaceful existence.
While Enterprise is on its way to investigate a planetary phenomenon near Earth, Mayweather gets a chance to visit his family on their cargo ship, but his homecoming is cut short when the ship is attacked by alien pirates. Meanwhile, aboard Enterprise, T'Pol and Phlox, who are horror-movie novices, are introduced to the unique human experience of watching the black and white version of Frankenstein with the rest of the crew.
Enterprise is asked to evacuate a group of Denobulan geologists from a world that has been taken over by a militant faction, and since they are located deep underground, the effort requires some treacherous spelunking by the rescue team. Meanwhile Phlox faces a dilemma when another evacuee, an Antaran afflicted with a fatal dose of radiation, refuses to be treated by a Denobulan because of very old bad blood between the two races.
While studying a star in the early stages of going supernova, Enterprise encounters a race called the Vissians. The two crews get along famously, until Trip Tucker gets a little too curious about a member of the species' third gender ? a nameless individual called a 'cogenitor'.
An arctic research team on Earth discovers debris from an alien vessel, nearly a century old, buried in a glacier along with the bodies of two cybernetically enhanced humanoids. Once those beings are thawed for investigation, they come to life and abduct the scientists and their transport vessel. Enterprise is called to intercept, but Captain Archer and his crew find these cyborgs to be an intractable, insidious enemy.
While Enterprise is investigating what appears to be a dark matter nebula, Archer receives news that A.G. Robinson, his old rival in the early days of the NX test program, has died. During a shuttlepod mission into the dark matter phenomenon, Archer reminisces to T'Pol about the time he and Robinson were pilots competing for the honor of being the first to break the Warp 2 barrier.
A Tellarite bounty hunter captures Archer intending to turn him over to the Klingons for a substantial reward. Meanwhile, T'Pol is infected with an alien pathogen that unleashes her primal Vulcan urges.
Earth is savagely attacked by a mysterious alien probe that leaves millions of people killed. When Archer learns that the culprit species is planning to destroy the entire planet with their next assault, Enterprise embarks on a new mission into the dangerous and highly mysterious Delphic Expanse to put a stop to it. Although T'Pol is given a direct order from the Vulcan High Command not to participate in this mission, she resigns her post in order to continue with Enterprise. Meanwhile, the Klingons, who are bent on destroying Archer, continue their hot pursuit of Enterprise all the way into the expanse.