Captain Archer and temporal agent Daniels have been stranded in the 31st century. In a library they investigate the damage to the time line and try to find way a to get Archer back in his own century. Meanwhile Silik the Suliban leader is trying his utmost to find the whereabouts of Archer and he is willing to go far for the answer. But the crew of Enterprise has plans of their own. Trip finds a way to use the com system and is able to speak with Reed. Together they try to contact other crew members and make plans to purge Enterprise of the Sulibans.
Celebrating T'Pol's one year anniversary as a member of the Enterprise's crew, Archer and Trip have dinner with her. Over dinner she tells them of the true first contact between Humans and Vulcans. It appears that her great-great-grandmother and a the crew of a scout ship crashed on Earth...in 1957.
The Enterprise stumbles into an area of space containing cloaked mines. When a malfunctioning, active mine attaches itself to a critical area of the ship's hull, Lieutenant Reed dons an EV suit and attempts to disarm it. Complications arise when the mine's leg penetrates Reed's leg, pinning him to the hull. Captian Archer must find a way to get rid of the mine and save Reed before the Romulans run out of patience.
After the encounter with the Romulan minefield, Enterprise is severely damaged. Engineer Trip fears the worst. With the ship only capable of warp 2.5, traveling back to Jupiter will take practically forever and he doesn't have the necessary components to make the repairs himself. Captain Archer decides to send out a distress call and it isn't long before he gets a response from the Tellarites. They give the coordinates of a strange repair station. Upon approaching Enterprise is scanned. The atmosphere and the docking port are automatically changed to Enterprise' specs...
After previously offending the Kreetassans, Enterprise attempts to make a better second impression, only to upset the alien race once again. A frustrated Captain Archer returns from the planet only to be further upset to find that his dog Porthos, has been affected by a pathogen native to the world. While Phlox works around the clock treating Porthos, Archer stands vigil in sickbay, experiencing first-hand the quirky everyday life of his Denobulan Doctor.
Upon returning from covertly observing a pre-warp culture, Lieutenant Reed realizes he lost his communicator somewhere on the planet. Archer and Reed return to recover the lost technology, only to find the natives found it first. Captured and interrogated, the crewmen find themselves doing even more damage to the culture, who have scanned the prisoners and know them to be of another race. Meanwhile, Tucker and Mayweather try to figure out how to active the cloak on the Suliban cell ship so they can mount a discreet rescue.
A mysterious wave is headed toward Enterprise. An alien shuttle warns the crew that the radiation will kill them and seeks shelter aboard ship. With only hours to prepare, ship's control is rerouted and Enterprise personnel take refuge in the highly-insulated, close-quartered catwalk. Soon it is discovered that the alien passengers are immune to the radiation and lied their way into hiding on Enterprise, which has been boarded and commandeered by aliens who assumed it to be abandoned.
Trip's shuttle is fired upon and he and his aggressor are forced to land on a nearby moon. While the nighttime weather is calm, the incoming dawn will make the planet inhospitable and deadly. Despite the language barrier and violent introduction, Trip and Zho'Kaan reach an understanding and struggle to survive, hoping to be rescued before the sun rises.
The Enterprise makes way to a planet hosting the Interspecies Medical Exchanges convention. Phlox seeks to take advantage of the opportunity to meet with Vulcan doctors to learn more about a highly-stigmatized neurological affliction only transmitted through Vulcan mind melds. The Vulcans discover T'Pol is afflicted. Believing the stigma to be unethical, T'Pol chooses not to reveal that her participation in the mind meld was not voluntary but the result of physical and mental assault. Meanwhile, Feezal, one of Phlox's wives is aboard to assist Trip in the installation...
Ensign Travis Mayweather takes leave when Enterprise rendez-vous with the cargo ship Horizon, his childhood home. The family reunion is bittersweet when Mayweather learns of his father's death and he butts heads with his brother/Acting Captain, Paul, who resents Travis' leaving the Horizon and finding a successful career with Starfleet. Meanwhile, Enterprise backtracks to visit a planet undergoing drastic geographical changes. T'Pol looks to avoid attending movie night.
At Dr. Phlox's request, Enterprise attempts to retrieve 3 Denobulan scientists from the planet Xantoras, where the Goverment has ordered all off-worlders to evacuate within 3 days. Tucker, Reed, and Mayweather navigate a series of labyrinthine underground caves in search of the scientists. Meanwhile, Enterprise lends assistance to a damaged ship fleeing the planet. Doctor Phlox faces an ethical dilemma when one of the refugees of the ship refuses life-saving treatment. The patient, an Antaran, holds a grudge against Phlox stemming from a war between their races that ...
Enterprise encounters a hyper-giant star. While there, they make first contact with the Vissians, a technologically sophisticated race with three genders. While making quick friends, and eagerly learning about the advanced technology, Trip gets curious about the Vissians third gender, known as the Cogenitor, who is crucial in the Vissian reproductive process. Against the wishes of the Vissians, Trip befriends the Cogenitor and encourages it to defy it's cultural boundarries, which the Vissians are made aware of, and are angered by.
Borg casualties from a century earlier (events depicted in "Star Trek: First Contact") are re-animated by a research team. The Enterprise is ordered to intercept them before they can escape in their commandeered ship.
While surveying an uninhabited planet, Enterprise is met by a Tellarite ship. Captain Archer is abducted by Skalaar, a Tellarite hoping to collect a bounty placed on Archer by the Klingons. Meanwhile, a microbe from the planet infects T'Pol and Phlox. The affliction causes T'Pol to prematurely enter Pon farr, a chemical imbalance invoking Vulcans urge to mate. Phlox tries to treat an emotionally unstable T'Pol, who is getting too close for Denobulan comfort.
An unknown probe fires on Earth from space, cutting a swath from Florida to Venezula. Everything in the path of the attack was destroyed, resulting in the deaths of seven million humans including Tucker's baby sister Elizabeth. Enterprise is recalled to Earth for upgrades to the ship and to take on military crewman. Silik give Archer a message from the future about Earth's latest enemy. The Klingon Empire gives Duras another chance to capture Archer. Enterprise heads for infamous and dangerous Delphic Expanse.