In the nine decades following Zefram Cochrane's visionary warp flight in space and the First Contact that followed, the human race has been slowly guided by the Vulcans toward developing the Warp Five engine. Mankind is at last able to explore the virgin depths of space with a revolutionary new starship, the Enterprise NX-01, under the command of Captain Jonathan Archer. Plans to launch Enterprise are moved up when a Klingon courier is shot down by unknown assailants and crash-lands in Broken Bow, Oklahoma. Feeling that the Vulcans have been condescending toward mankind for years, Archer insists it's the humans' responsibility to return the injured Klingon to his homeworld alive. Archer is fully backed by Starfleet Command, and the Vulcans' objections fall upon deaf ears.
With the ship high above Earth in spacedock, Archer has three days to assemble his crew, consisting of the charming southern chief engineer, Commander Charles "Trip" Tucker III; the strong and wary tactical officer, Lieutenant Malcolm Reed; the eager helmsman who grew up in space, Ensign Travis Mayweather; the linguistically talented communications officer, Ensign Hoshi Sato; and for his chief medical officer, Archer recruits the unconventional alien Dr. Phlox. For the ship's first mission, the Vulcans request that an advisor from their ranks be present, and they assign the highly intelligent but stubborn Sub-commander T'Pol. Anticipation and nerves run high as the ship is fitted with the latest Starfleet technology, such as the recently approved transporter, which no one is very eager to test on themselves. Quickly the historic launch arrives, and the Starship Enterprise does indeed, in the words of Dr. Cochrane, "go boldly where no man has gone before," warping towards planet Kronos.
As Enterprise speeds along her way, the crew all learn more about each other and strong bonds begin to form. Under Dr. Phlox's care, the injured Klingon, Klaang, regains consciousness and Hoshi tries to communicate with him. Suddenly the ship experiences a power failure and unknown chameleon-like aliens invade and kidnap Klaang from Sickbay. Dr. Phlox examines a captured alien and discovers he's a Suliban who has been genetically altered. With the Klingon gone, T'Pol advises Archer to return the ship to Earth, but he adamantly refuses. He then learns from the tight-lipped Vulcan that Klaang's last stop before crashing on Earth was a planet called Rigel X, so Archer orders Mayweather to set a course for the Rigel system. Meanwhile, a Suliban named Silik interrogates Klaang, trying to find out why he was on Rigel X meeting with a Suliban female named Sarin. At Rigel X, the Enterprise away team discovers an amazing multitude of alien life at a trading complex there, and their attempts to locate information on Klaang's visit are constantly interrupted by strange new sights and sounds. Archer eventually meets Sarin, who tells him of a Temporal Cold War in which the Suliban are being used to incite internal strife within the Klingon Empire. Klaang was bringing proof of this back to his High Council in order to avoid the Empire being thrown into chaos. Hidden Suliban soldiers suddenly attack, forcing Archer, Sarin and the rest of the away team to fight their way back to Enterprise. During the extremely intense firefight Sarin is killed, and later Archer is rendered unconscious from a deep blast to his leg while saving T'Pol's life.
As Archer recovers, T'Pol takes command of Enterprise despite Trip's objections, and astonishes everyone by enabling 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, or "Helix" with 3000 lifesigns on board. They are attacked by several individual Suliban cell ships, but manage to capture one with the ship's grappler. Archer and Tucker learn to fly the stolen craft and use it to infiltrate the Helix while Enterprise hides in a dense upper layer of the atmosphere and avoids the Suliban's depth charges. Archer and Tucker find Klaang and release him while fending off the Suliban with their new phase-pistols. While Tucker takes the Klingon back to Enterprise, Archer stays behind to set off a magnetic disruptor that dismantles the Helix. Trying to stay alive while waiting for pick-up, Archer discovers a Temporal Chamber used by the Suliban to obtain their orders from a mysterious shrouded figure from the future. Archer is found by the Suliban leader, Silik, and the two struggle against each other in a time-shifted environment. Realizing he's no match for the genetically mutated Suliban, Archer tries to gain some distance by exiting the chamber, where time returns to normal. As Archer runs, Silik fires his weapon dead center into Archer, but at that moment the captain dematerializes, being unwittingly beamed back to Enterprise by a nervous Tucker using the relatively untried bio-transporter.
Leaving the Suliban behind, Enterprise warps away and successfully delivers Klaang to his homeworld. The Klingon Chancellor draws blood from Klaang, and his scientists find hidden within his DNA the Suliban data proving their conspiracy to undermine the Empire. The Chancellor turns to Archer and acts hostile toward him, but Archer takes his actions as a "thank you."
Back aboard Enterprise, Archer receives orders from Starfleet that henceforth, he and his crew are to officially begin their mission of exploration. Gratefully acknowledging her assistance in the mission's success, Archer sets aside his pride and convinces T'Pol to remain on the ship as Science Officer. A course is laid in for the nearest inhabited planet, and the crew of Enterprise boldly warps toward the unknown.