The Enterprise, under Captain Jonathan Archer, sets off on its maiden voyage with a mission to return a wounded Klingon to his people.

As they continue their deep space exploration, the Enterprise crew comes across an alien ship where they discover 15 humanoid corpses that seem to have been part of a scientific experiment. The horrific sight inspires Hoshi to panic and demand a return to Earth, but Archer insists on continuing the mission and finding out more about the abandoned dead. Trouble comes calling when the aliens that were conducting the gruesome experiments return and begin attacking Captain Archer and his team.

When the Enterprise investigates an uninhabited planet that turns out to be far more dangerous than expected. The crew members that visit the planet are infected by an alien pollen that induces hallucinations and paranoia.

When Trip is dispatched to assist an alien ship with its power source problems, he is delighted to have a friendly encounter with one of the ship's female engineers. But after discovering that their special moment has resulted in his becoming pregnant, he realizes he's had an unwitting experience with alien sex. Archer and his crew must then try and return the rapidly growing alien baby to its mother.

The Enterprise crew alters course to investigate the mystery of Terra Nova, a legendary Earth colony whose inhabitants mysteriously disappeared decades ago. But when they arrive, they confront descendents of the colonists who have become more alien than Archer could ever have imagined.

The Enterprise crew pays a friendly visit to an ancient Vulcan spiritual sanctuary, despite T'Pol's concerns that her human colleagues will be an awkward and disruptive presence there. Upon landing, they discover that the monastery has been forcibly taken over by the Andorians, a paranoid and highly excitable race of aliens with a long history of conflict with the Vulcans. Archer soon discovers that the Enterprise crew has gotten in the middle of an interstellar Pandora's Box and now must find a way out.

A Vulcan starship interferes with Archer's probe of an oversized comet.

Captain Archer and the crew discover a fully inhabited, civilized though less advanced Earth-like planet. Disguised to look like its inhabitants, they pay the planet an exploratory visit where they learn that a pernicious illness is afflicting the local population. As Archer seeks to help them find the malady's source, he finds himself in a close encounter with a comely female alien.

The Enterprise crew is dispatched by Starfleet Command to assist Fortunate, a human freight vessel that has been attacked by Nausicaan pirates. On arriving, they are surprised to find that Fortunate's crew is resistant to Archer's efforts to help them and determined to seek revenge against their attackers, no matter what the repercussions.

When the Enterprise comes in contact with an alien vessel transporting stargazers to observe a spectacular stellar event, Archer invites them aboard the ship not realizing that Silik, a Suliban enemy, is among them. Archer quickly realizes that Silik is engaged in a nefarious time-travelling mission and must stop him before he can tamper with the course of history.

When Enterprise is attacked by an unidentified enemy ship, the crew must work frantically to get their new phase canons to operate. Meanwhile, Archer realizes that no one knows Reed well enough to give him a personalized birthday gift.

The crew discovers a new planet with two races, one in desperate need of medical and scientific assistance. In the course of trying to help, Dr. Phlox recalls his own Denobulan past to address the ethical dilemmas that arise in the present.

When Enterprise comes across a wounded Klingon vessel, T'Pol, Hoshi and Reed take a shuttlepod down to investigate. There they are ambushed by a hostile female Klingon who hijacks the shuttlepod, leaving the Enterprise crewmembers dangerously stranded aboard the Klingon vessel. Now it's up to Archer to take the Klingon under guard and enlist her help in rescuing his crew.

Archer and the crew are disappointed to discover that T'Pol has been ordered by the Vulcan High Command to leave Enterprise -and equally frustrated at her seeming indifference to leaving their ranks. T'Pol's last mission as a Starfleet officer, however, proves eventful when she and Archer are kidnapped by a militant faction on an alien planet. However, aid comes to them in the form of the Andorians: their leader, Shran, still owes Archer a debt (from the events of "The Andorian Incident"). It turns out the Vulcans are covertly backing the ruling faction on the planet, while the Andorians are aiding the freedom fighters. With the help of the Andorians, Malcolm and Trip rescue Archer and T'Pol over the objections of the local Vulcan ship, and Shran considers his debt to Archer repaid.

Tucker and Reed set out on a mission in a shuttlepod, as Enterprise is busy investigating an asteroid field. Disaster strikes while the pair are away, leaving the shuttlepod damaged and the warp drive inoperable. They manage to make it back to the rendezvous coordinates only to discover Enterprise was apparently destroyed when it crashed into an asteroid. With the ship seemingly no more, the pair are left abandoned in the middle of nowhere with only a few days of air remaining.

The Enterprise encounters a group of Vulcan civilians who have split off from the normal way of Vulcan life in an effort to explore their emotions. T'Pol is disturbed by the new visitors and warns the Captain that all attempts in the past to integrate Vulcan emotions into their lives has proven disasterous. Meanwhile a message from Admiral Forrest leaves the Captain with the difficult task of trying to convince one of the visiting Vulcans to call home to speak with his dying father.

While exploring an uncharted planet, Enterprise crew members encounter a group of aliens who are hunting down indigenous creatures for recreation. During their exploration, Archer is mesmerized by visions of a woman desperately attempting to communicate with him. The woman's ethereal distress signal informs Archer that she and others like her are actually the prey of the alien hunters. Heeding her call, Archer levels the playing field against the alien hunters.

The Enterprise encounters Ferengi pirates who use gas to knock out the crew and look for treasures on the Enterprise. But they haven't counted on Tucker, who happens to be in the decon chamber and avoids the gas, and attempts to win back the ship from the pirates.

While exploring a crashed vessel on a desolate planet, the Enterprise crew is haunted by some ghostly figures, and they encounter an alien race that has survived despite insurmountable odds. Trip helps repair their derelict vessel and is befriended by Liana, an attractive humanoid alien who develops feelings for him.

While exploring a planet, Archer and Mayweather enter a "military zone" and are detained in an internment prison by an alien race called Tandarans, who are at war with the Suliban. While the Enterprise crew's previous encounters with the Suliban have been disastrous, Archer and Mayweather find themselves sharing a cell with some Suliban detainees who they believe may be wrongly imprisoned.

A strange, symbiotic alien creature boards the Enterprise capturing a few of the crew members, including Archer and Trip, and cocoons them in its web feeding off their bodies to survive. With the captured crewmembers' lives in jeopardy, Hoshi, under T'Pol's command, faces her biggest challenge by trying to find a way to communicate with the lifeform in order to return it to its home planet.

The Enterprise is sent to the planet Mazar to pick up a Vulcan ambassador expelled for misconduct.

When Archer and Trip are invited to a desert-like planet by an alien leader, after they help fix his ship, discover he is a terrorist who has lured them onto his planet under false pretenses. Meanwhile, T'Pol, while in command, faces a tough decision when she cannot locate Archer and Trip in the desert.

When the crew takes shore leave on the famous pleasure planet of Risa, Archer has a mysterious encounter with an alien woman; Hoshi has a surprising romantic rendezvous; Mayweather has a rock-climbing accident; and Trip and Reed go clubbing only to end the evening as unwitting victims of robbery. Meanwhile, Phlox stays on board the Enterprise with T'Pol to take his annual 48-hour hibernation and exhibits some uncharacteristic oddities when they have to wake him up after an injured crew member returns from shore leave.

Starfleet orders Enterprise to return home when the crew seemingly causes the destruction of an alien planet they were exploring. Archer is visited by former crew member Daniels, who traveled through time to warn him that the Suliban are trying to sabotage Enterprise's mission, and the two travel through time to try to thwart the Suliban's plans.