Following the destruction of the Xindi weapon, the Enterprise crew discovers that they have been sent back in time to 1944. However, history has been altered, leaving Nazi Germany in control of a large portion of the eastern United States.
After Silik attacks Trip, Vosk wants to make a deal with Archer: supplies of the ship for the completion of his time machine in return for a trip to the 22nd Century.
The crew take some time off. Archer meets an old friend, Captain Erika Hernandez. T'Pol takes Trip to Vulcan, with a surprise waiting. Phlox finds out Earth has become xenophobic.
After a Klingon ship is attacked, it's discovered the imprisoned Dr. Soong's genetically enhanced humans are responsible. Archer takes him to prevent a war.
After a bombing destroyed the Earth embassy on Vulcan, a group known as the Syrrannites are suspected. T'Pol receives a map from her Syrrannite mother, leading into a dangerous desert, the Forge.
T'Pol and Archer confront the Syrrannites and meet T'Pau who denies the embassy bombing. Archer, who has Surak's essence, is asked to help. V'Las threatens Enterprise to make sure an attack on the Syrrannites isn't witnessed.
Noncorporeal aliens inhabit the bodies of Enterprise crew members to study how the crew reacts to a lethal virus infection that has afflicted Trip and Hoshi.
Enterprise escorts Tellarites to peace talks with Andorians. While transporting they rescue Andorians and say the Tellarites attacked them. Enterprise is soon attacked by an Andorian ship, and Archer must prove who is responsible.
While Enterprise is visiting Earth, Phlox is abducted by the Klingons and forced to research a cure for a virus destined to wipe out the race. Reed is tapped by a secret agency and ordered to betray Archer. Trip transfers to the Columbia.
While Enterprise tries to bring Trip on board to reverse the malicious Klingon modifications, Phlox and Antaak find a cure for the virus that will not please General K'Vagh.
Set in the dark and oppressive Mirror Universe, Commander Archer leads a mutiny in a bold attempt to seize control of an advanced starship - a vessel from the future that may be the key to saving the Terran Empire.
The Mirror Universe saga concludes as Archer declares himself captain of a formidable starship from the future, while his alien crew launch a rebellion in a desperate bid to keep him from achieving ultimate power.
While attending a conference on a proposed interplanetary alliance, Trip and T'Pol find out from a dying woman that they have a baby. Investigation shows the woman was a member of the xenophobic organization Terra Prime.
Paxton threatens to destroy Starfleet Headquarters if all aliens don't leave Earth. Enterprise must shut down the verteron array on Mars, but it is extremely well defended.