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.
On the first anniversary of her assignment to Enterprise, T'Pol tells Archer and Trip about the first contact between humans and Vulcans, which involves three Vulcans becoming stranded in the town of Carbon Creek, Pennsylvania in 1957.
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.
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 boundaries, which the Vissians are made aware of, and are angered by.
An unknown probe fires on Earth from space, cutting a swath from Florida to Venezuela. Everything in the path of the attack was destroyed, resulting in the deaths of seven million humans including Tucker's younger sister Elizabeth. Enterprise is recalled to Earth for upgrades to the ship and to take on military crewmen. Silik gives 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.