A hundred years after the events of the film First Contact, interaction between the Vulcans and humans has resulted in a permanent Vulcan presence on Earth. But the Vulcans have not been entirely generous in sharing information and technology, and mankind is still being held back. When a lone Klingon crash lands in Broken Bow, Oklahoma?the first ever seen by humans?a series of events transpires that thrusts mankind into deep space for the first time. Once en route to Kronos, the Enterprise encounters a genetically altered time traveling race called the Suliban, who are apparently involved in some sort of temporal cold war using the unwitting Klingons as pawns. The Enterprise crew must see Klaang, the Klingon who crashed on Earth, safely back to Kronos to avert a Klingon civil war.
After T'Pol takes command of Enterprise she enables the ship to track the Suliban vessel from Rigel X, rather than ordering the ship back to Earth. After Archer resumes command they arrive at a gas giant planet, apparently losing the Suliban's trail. But T'Pol is again surprisingly helpful when she works with Archer to determine that not one but 14 Suliban vessels have recently entered the planet's atmosphere. Enterprise goes in to follow and discovers a huge Suliban mothership. They are attacked by several individual Suliban cell ships, but manage to capture one. The crew then has to learn to fly the stolen craft and use it to infiltrate the Helix.
As they continue their deep space exploration, the NX-01 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 Sato 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.
Tucker, Mayweather and T'Pol go on a research mission to a seemingly uninhabited Earth-like planet where they become infected with hallucinogenic flower pollen that sends their imaginations into a state of paranoid overdrive. When a violent storm strands them on the planet, Archer must find a way to save them before they turn dangerously on one another.
When Tucker 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. Now it's up to the Archer and the crew to 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 descendants 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.
Trip learns that T'Pol is transmitting secret messages to a Vulcan ship, which has been shadowing Enterprise for weeks. Meanwhile, Archer must attempt a dangerous rescue to recover two crewman stranded on a rapidly disintegrating 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 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 encounters an alien race in desperate need of medical and scientific assistance. Phlox declines to assist them because of his ethical beliefs leaving Archer to decide whether to help them find their own solutions.
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 the 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 and find themselves once again at the mercy of the volatile Andorians.
On a routine shuttlepod mission to investigate an asteroid field, Trip and Reed find themselves suddenly cut off from the Enterprise and become convinced that the mothership has been destroyed. With a limited oxygen supply and almost no chance of being rescued, the opposite-minded twosome must battle their annoyance with one another while also coming to terms with their impending demise.
The Enterprise hosts a group of Vulcans who, unlike T'Pol and the other Vulcan High Command, are eager to embrace and experience their own emotions. When one of their rank tempts her to adapt their more free-spirited approach to life, T'Pol finds herself faced with a confusing and intriguing dilemma.
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.
When the Ferengi, a group of intergalactic thieves, stun the Enterprise crew and try to rob the ship, it?s up to Trip to work covertly to stop them. After the Ferengi awaken the Captain to force his assistance in pillaging his ship, Trip secretly reveals to Archer that he has inadvertently escaped the effects of the noxious gas and they work together to try to surreptitiously thwart the robbery and save the crew.
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.
When a Vulcan ambassador is accused of secretive criminal misconduct, Enterprise is asked to transport her back to the Vulcans. Following an attack by a corrupt alien race, T'Pol defends the Ambassador and, for the first time, asks Archer for his help. Meanwhile, after the Vulcan diplomat boards the Enterprise, alien weapons begin firing from hostile ships, putting everyone's lives at risk.
When Archer and Trip are invited to a desert-like planet by an alien leader after they help fix his ship, they 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.