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

Captain Archer wants to convert curiosity into deeds and decides to enter a ship floating in space. Hoshi has trouble adjusting to life on Enterprise.

When Trip is dispatched to assist a Xyrillian ship with its power source problems, he is delighted to have a friendly encounter with one of the ship's female engineers. However, shortly after returning to Enterprise, he discovers that their seemingly innocuous interaction has led to a surprising result.

Enterprise visits 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.

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.

Starfleet orders Enterprise to return home when the crew seemingly causes the destruction of an alien planet. However, a visit from Crewman Daniels leads Archer to believe that this disaster was the plot of one of the factions from the temporal cold war.

Daniels and Archer must find a way back to the 22nd century in order to make sure history plays out as it should. Meanwhile, on board Enterprise, the Suliban have taken over the ship, but Reed, Trip, and T'Pol formulate a plan to eject the aliens.

Archer spends a night in sickbay with Dr. Phlox after Porthos contracts a deadly virus on the Kreetassan homeworld. Crew members suspect Archer's increased stress level is due to Porthos' illness, but Dr. Phlox suspects it has to do with Archer's repressed sexual tension.

In need of fuel, the Enterprise arrives at a Quonset mining colony for deuterium supplies. They discover that Klingons are forcing the colonists to give up all their deuterium. Archer and the rest of the crew work to train the colonists so they can fight back against the Klingons.

Archer, Mayweather and T'Pol travel to an arctic world to apprehend a fugitive, when T'Pol is contacted by Vulcan High Command. The mission takes a dangerous turn when T'Pol begins having flashbacks that suggest the events she remembers about a former mission may not accurately relate to what happened.

Archer and Reed return to a pre-warp society, that is on the verge of war, to recover a lost communicator from an undercover survey mission.

Hoshi experiences her first transporter experience and strange aftereffects lead her to believe she wasn't reassembled correctly.

Enterprise visits a planet where an Interspecies Medical Exchange conference is being held. Dr. Phlox tries to obtain research on a terminal disease from the Vulcan contingency, without revealing T'Pol has been infected by it.

Noncorporeal aliens possess the bodies of the Enterprise crew.

The Enterprise crew makes first contact with the Vissians, a species with three genders. Trip meets one of the species' third gender, known as Cogenitor, and learns how badly Vissians treat all Cogenitors. Trip attempts to help the Cogenitor, even though it interferes with Vissian culture.

An alien race known as the Xindi launch an attack on Earth, causing great casualties and massive damage. As Enterprise heads back home, an unlikely source informs Archer about the Xindi and that their next attack will destroy Earth.

Captain Archer and his crew set out to gain information about the mysterious and antagonistic Xindi race.

Archer and T'Pol travel back in time to 2004 Detroit to stop a Xindi plot.

Archer sets out on a suicide mission to destroy the Xindi superweapon as Enterprise faces a brutal attack.

Archer puts his life on the line in a risky gambit to intercept the Xindi superweapon and disarm it from within.

Six years in the future, an emotional Captain Archer and the crew return to Earth to face the decommission of Enterprise and signing of the Federation charter.