Aliens have arrived and devastated human civilization. The survivors have gathered into a resistance, including history professor Tom Mason. Mason has been assigned as second in command for the 2nd Massachusetts, but his primary focus is his three children, one of which has been captured by the aliens.
Tom is assigned the task of searching an abandoned armory for possible weapons. During the search, his team is attacked and captured by a gang whose leader ransom's them for the 2nd Mass cache of weapons.
A doctor arrives at the 2nd Mass with a procedure to remove the harnesses from the children. Tom leads a team to rescue his son from the skitters and mechs but the result is not what he planned.
Tom's next assignment is to acquire additional motorcycles for scouting purposes. Weaver sends Pope along over Tom's objections, and his fears are validated when the team is assaulted at a motorcycle store. Anne and Dr. Harris butt heads over the task of gaining intelligence from the captured alien.
Tom and Hal infiltrate a skitter's lair to rescue Ben and the other kidnapped kids. Anne's anger after a tragedy leads to a surprising discovery about an alien weakness.
The 2nd Mass must decide whether to accept another militia leader's offer of sanctuary for their children when news of an alien attack reaches them.
Mike discovers something is wrong at the sanctuary, and Hal becomes the children's protector. Anne's pregnant patient begins labor just while the 2nd Mass is evacuating.
Tom has misgivings about Weaver's behavior as the 2nd Mass prepares for the offensive. While scouting, Tom, Hal and Weaver meet a woman living alone in the abandoned city, and they are unsure about whether she can be trusted. They also sight Karen again.
Tensions between Tom and Weaver threaten the fighting cohesiveness of the 2nd Mass. Anne's discovery about the alien's origins confound Tom. Uncle Scott's experiments affect Ben and Rick.
Weaver leads volunteers to attack the aliens while Tom stays to protect the civilians. Rick escapes to return to the aliens which endangers everyone since he knows the 2nd Mass battle plan.
Three months have passed since Tom Mason agreed to leave on an alien ship. Capt. Weaver still holds military command of the 2nd Mass, while Anne has become the group's lead doctor. For his part, Pope has assembled a group of rebellious renegades within the colony dubbed the 'Berserkers'. This new order is thrown into chaos when Tom suddenly returns without warning, to the shock and skepticism of his former comrades.
Tom is haunted by memories of his captivity on the ship, and begins to wonder if his mind has been tampered with. Pope does nothing to help Tom's cause, planting seeds of doubt among the 2nd Mass. Advance military scouts discovers an old bridge that could facilitate the group's escape from an impending attack, but it may be too late to make a difference.
The 2nd Mass seeks refuge inside an empty airport hanger, but Anne worries that the conditions could be hazardous to the group's health. Meanwhile, Pope and his Berseker squad actively conspire to oust Tom. Also, the collective mourning period for a lost friend is interrupted by the arrival of an unexpected visitor carrying a message of hope.
Ben and Hal's bikes get stolen while on patrol, and the hunt for the culprit leads them to a previously unknown group of teenage survivors. Capt. Weaver is shocked to discover that one of the survivors is his thought dead daughter Jeanne. The teens' leader Diego initially accepts the 2nd Mass' offer of food and shelter, but a disagreement about strategy creates conflict.
The group is stunned when the formerly harnessed Rick returns. Despite his previous betrayal, Rick claims to mean the 2nd Mass no harm. Meanwhile, a captured alien tells tales of a skitter rebellion against the invaders, but Tom and Weaver it hard to accept as true. Also, Hal and Maggie grow ever closer.
Hal stumbles upon the bodies of several formerly harnessed kids, only to find his ex-girlfriend Karen alive among the rubble. Hal wants to give her the benefit of the doubt, but the 2nd Mass is understandably wary. Meanwhile, Weaver becomes increasingly ill, seemingly the victim of an alien made pathogen.
Ben makes the mistake of buying into Karen's lies, and quickly finds himself in mortal danger. Or at least it would appear that way until the cavalry arrives to take down the alien overlord threatening him. The 2nd Mass' triumph is short lived though, as Karen returns with an all new variation of the enemy.
The 2nd Mass continues the long, arduous journey to Charleston. Group morale is at an all time low after recent devastating losses, lending an air of somberness to the proceedings. Also, Weaver learns more about what Tector did prior to the invasion, and Maggie reveals her secret past to Hal.
The 2nd Mass finally arrives in the safety of Charleston. Tom is surprised to find his old mentor Arthur Manchester serving as leader of the colony. Everything seems happy until Manchester's true agenda is revealed. When the 2nd Mass and the Berserkers refuse his demands, he orders military commanders to throw them in the brig.
Following the military coup against Arthur Manchester, a representative of the rebel skitters approaches Charleston with a plan to take down the enemy. The 2nd Mass is receptive to the idea, but Charleston's military leaders disagree. In the end, Tom, Hal, Anne, Weaver, and Ben head out to get the job done.
Seven months following the events of season two, the 2nd Mass has made Charleston into their home. Tom has been elected president of the new United States, and humanity has begun to make headway against its otherworldly enemy. The main reason for this is the arrival of a friendly alien race called the Volm, which have a standing grudge against the evil Espheni. Meanwhile, the hunt is on for a spy in the colony, and Hal is plagued by strange dreams.
A little bundle of joy arrives in Charleston, as Tom and Ann celebrate the birth of their daughter Alexis. All is not happy however, as battles between humanity and the Espheni continue to escalate. In a desperate bid to cut off an enemy power source, Tom enlists the help of an reclusive nuclear scientist named Dr. Roger Kadar. Elsewhere, the spy takes out of a member of the colony, and Hal's dreams of Karen intensify.
With the two-year anniversary of the Espheni invasion looming on the horizon, the 2nd Mass finds itself under attack from an entirely unexpected threat. Elsewhere, Anne becomes more and more worried that her baby may not be entirely human, but Lourdes suspects it may simply be postpartum psychosis. Also, Hal begins to suspect he himself might be the spy everyone is looking for.
Following a successful defense of Charleston from an Espheni attack, Tom joins new arrival Lt. Fisher, Gen. Bressler, Pope, and Volm ally Cochise on a top secret mission to make contact with still living U.S. President Benjamin Hathaway. Meanwhile, Anne has DNA tests performed on Alexis, Hal fights to keep control over his own mind, and Ben can't decide whether to remove his harness spikes or not.
Tom awakens after the plane crash to find Bressler dead, and Pope unconscious. Tom drags Pope to safety, but both men are now stranded far from Charleston, with the Espheni on their tails. Back at camp, Weaver leads a search party looking for Anne and Alexis. Marina and Dr. Kadar grow steadily more suspicious of the Volm's secret weapon.
Tom demands to head out on a rescue mission to find Anne and Alexis, but before he can go, Hal's dark side finally makes itself known publicly. The implant controlled Mason takes his dad hostage, leading to a tense stand-off. The rebel skitters offer a risky solution to Hal's problem, one he may not live through. Also, Charleston's government experiences a major shake-up.
The Masons journey to rescue Anne and Alexis is interrupted by a surprise attack. A family called the Picketts robs and threatens them, leading to a family vs. family battle over the Masons' needed supplies and horses. Meanwhile, suspicions about the Volm weapon intensify, a barely alive President Hathaway is returned to Charleston by Cochise, and the true identity of the mole is revealed.
Tom awakens to find himself in a world he doesn't understand. Tom's wife is alive, and the invasion never happened. Everything seems perfect, that is until Tom begins receiving messages from someone named Anne Glass. Is Tom's dream world real, or simply Espheni mind games? Meanwhile back at Charleston, Pope and Weaver differ on how to handle the hunt for President Hathaway's killer.
Tom returns to Charleston, complete with new information on where the Espheni are vulnerable to attack.
Sadly, he also informs that Anne and Alexis are believed to be dead. Things are thrown into chaos when first the Volm complex and then Charleston are damaged by large explosions. Can Tom finally figure out the identity of the mole before it's too late?
The 2nd Mass celebrates a crucial victory against the Espheni, only to be shocked by the new plans of their allies the Volm. The advanced alien species has decided to ship humanity off to camps in Brazil, for their own safety. Naturally, Tom, Weaver, Pope and crew are having none of it. Also, Tom wages a final battle with Karen, and learns a shocking truth about Anne and Alexis.