Echo is a member of a highly illegal and underground group of individuals whose personalities have been wiped clean so they can be imprinted with any number of new personas. Confined between missions to a secret facility known as the Dollhouse, the "Actives" are hired by the wealthy, powerful and connected to wholly become—with mind, personality and physiology—whomever the client wants or needs them to be. They know no other life than the specific engagements they are in at that time—or do they?
It has been several months since Alpha's reign of terror and Echo, who is now randomly picking up flashes of past engagements, weds a British businessman who has ties to one of Ballard's open FBI cases. Topher becomes the target of Dr. Saunder's aggression after she finds out that she is actually a doll named Whiskey. Boyd takes on a risky venture and mixes business with pleasure, while DeWitt makes Ballard an irresistible offer.
Echo is imprinted with the personality of a mother with a newborn baby. Complications arise when, thanks to Topher's programming, Echo takes too strongly to motherhood. Perrin ramps up his investigation into Rossum and DeWitt pays November a visit.
Echo and Victor’s imprints collide when Echo is sent on an assignment as a fun-loving, seductive college student and Victor is imprinted as the psychotic nephew of a Dollhouse shareholder.
Sierra is forced to face her past as her connection to the Rossum Corporation leads to obsession and murder.
When Senator Perrin makes his stand against the Rossum Corporation, Echo attempts to stop his expose. Adelle, and Topher begin to see what they are up against in the rival of Washington DC.
Echo and Bennett have a shocking meeting as Adelle goes head-to-head with the ruthless head of the DC Dollhouse. Topher sees double when he must involve Victor in his espionage. Perrin finds a surprising witness to testify against the Rossum Corporation, but find he may be living in a house of cards.
After her entanglements with Senator Perrin and the DC Dollhouse, Echo finds herself out in the world-at-large as she struggles to control her multiple memory downloads. Topher discovers the dangers of science that will have devastating effects on the future, while Adelle engages in a power struggle with Harding.
When Echo's past romantic engagements are found murdered, the Dollhouse fears that Alpha has returned to seek his revenge. Adelle grows suspicious of Ballard who hopes to find allies in Boyd and Topher. The Actives turn against their handlers, leaving one member of the house permanently mind-wiped.
As his contract with the Dollhouse expires, Victor is released back into the world, where his military past threatens his future with Sierra. Meanwhile, Echo is deemed too dangerous and is sent into her worst nightmare.
When Adelle, Boyd, and the rest of the Dollhouse fear that Echo's uncontrollable mind imprints are making her a danger to their goals, they send her to "the Attic" where Echo is forced to face her worst nightmare in order to survive.
Topher races to reconstruct Echo's original personality and memories when Adelle realizes they are the key to averting a devastating future. Meanwhile, Echo and Bennett's shared past and the identity of The Rossum Corporation's mysterious leader are revealed.
Sacrifices are made when Echo leads her crew to Arizona to dismantle the Rossum Corporation's mainframe.
In the year 2020, Echo and her surviving Dollhouse crew attempt to restore order to a devastating future world before mankind is eliminated.