After the horrifying revelations and reversals of fortune in Baltimore, Chandler and his fractured team join forces with an underground resistance in an attempt to defeat Amy Granderson. With doses of the cure running low, Rachel tries to do some good for the sick while remaining a prisoner at Avocet. Meanwhile, Slattery and the crew of Nathan James are in a race against time to save an injured Dr. Tophet and regain control of their ship.

After the horrifying revelations and reversals of fortune in Baltimore, Chandler and his fractured team join forces with an underground resistance in an attempt to defeat Amy Granderson. With doses of the cure running low, Rachel tries to do some good for the sick while remaining a prisoner at Avocet. Meanwhile, Slattery and the crew of Nathan James are in a race against time to save an injured Dr. Tophet and regain control of their ship.

Nathan James returns home to Norfolk on a mission. With his family now safely aboard the James, Chandler sends his crew in search of their friends and loved ones.

The crew of Nathan James discovers that hospital ship USNS Solace was sent to sea to wait for Dr. Scott's cure. Captain Chandler sees an opportunity to add another ship to their fleet while Rachel is eager to find a lab better equipped to replicate the vaccine. When Solace fails to respond to radio communications, Chandler and his team board the ship...and come face-to-face with an unexpected enemy.

With a small group of survivors from Solace in tow, Chandler and his crew square off against an enemy of the most dangerous kind - a nuclear-powered submarine led by rogue British naval officers, Sean and Ned Ramsey. XO Slattery interrogates a captured mercenary from the hospital ship in an effort to extract information on the sub and its mission. As Nathan James engages in a perilous game of cat-and- mouse, the truth about the mercenary sub unfolds.

Chandler tracks a new threat to Northern Florida. Meanwhile, Rachel comes across a secret formula that her mentor, Dr. Hunter, had been perfecting.

While XO Slattery struggles to evade the sub in the water, Chandler and the land team infiltrate the Immune compound. Danny poses as one of Ned's workers and discovers that Niels, a.k.a. Patient Zero, is now working for the Ramseys. Meanwhile, Captain Chandler manages to encroach on Sean's inner circle, which includes an important government official, Jeffrey Michener. Has Michener been brainwashed by the Immune propaganda along with the rest of the camp? Or can he be an ally?

Still trying to piece together Dr. Hunter's lost formula, Rachel grapples with the fact that Niels, her sworn enemy, is now on board Nathan James, while Chandler works to gain intel and reverse the brainwashing Michener suffered at the hands of the Ramseys.

With Dr. Scott on the verge of a breakthrough, Chandler and his team set out to land in search of much needed supplies and materials for her lab.

Rachel is hard at work on a new, more efficient version of the cure while Alisha decodes a message found on a recovered cell phone.

After a message is broadcast implicating the Navy in a devastating disaster, Chandler looks to infiltrate the network and regain the trust of the American people.

After retrieving the mastermind behind the Immune communications network, Nathan James finds itself trapped between the sub and civilian blockades set up by the Immunes. Chandler sends Dr. Scott and the cure off the ship under the protection of XO Slattery as the James heads towards its inevitable final showdown with the sub.

Season Finale- With their mission now fully dedicated to spreading the cure, Nathan James puts a call out to civilians to meet at pre-selected ports across the country, where all will receive the cure. However, small Immune factions remain active in their quest to fight the cure and fulfill Ramsey's dreams.

Captain Tom Chandler and the crew of the USS Nathan James set out for the Arctic with two civilian virologists, Dr. Rachel Scott and Dr. Quincy Tophet, who claim to be studying birds. When they come under attack by a renegade team of Russian forces, Chandler learns these virologists are actually collecting samples of the source of a deadly virus that has wiped out over half the human population while they've been at sea. As they head home on the orders of the remaining U.S. government, Chandler and his crew realize that home is a shadow of what they left, and the safest place to develop a vaccine for this deadly disease is out at sea on their ship.

Chandler and his crew head to the U.S. Military base at Guantanamo Bay in hopes of collecting food, medical supplies and fuel replenishments. Three teams are dispatched to carry out these varied tasks. While there, they come under attack by escaped Gitmo prisoners and enlist the help of a grizzled private contractor who's been surviving for weeks and living off the land.

The James faces off against a new foe who demands Chandler hand over Rachel and her research. When Chandler refuses, he and his crew are put to the test as Chandler engages in a series of risky strategic moves. But it turns out their new enemy has his own horse in the race to find a cure for the virus..

Days after a trying series of events at Gitmo, Chandler and his crew are put under extreme duress when the ship's propulsion system suffers a catastrophic event. With Dr. Scott in danger of losing all her research on the virus and a crew overworked, overtired and desperately low on drinking water, Chandler’s leadership and ingenuity are put to the test.

With Rachel close to a breakthrough on her vaccine, she, Chandler and XO Slattery lead a small team into the jungles of Nicaragua on a mission to find monkeys for her vaccine trials. While there, they find much more than they bargained for when they run across a former drug kingpin who will stop at nothing to maintain his stranglehold on his oppressed society. Chandler and his men find themselves in a huge moral dilemma over whether to eliminate this menace or take what they need and continue on with their mission.

After returning from the horrors of Nicaragua, panic begins to spread throughout the ship when Lt. Danny Green comes down with a mysterious illness that could be the virus. Losing faith in Rachel and her failing vaccine trials, Chandler now has to deal with a restive crew. If he fails to keep the crew together, the whole mission is in jeopardy.

After picking up a distress call near Jamaica, Chandler and a small team stage a rescue attempt. But a surprise attack leave Chandler and Tex stranded at sea. Slattery and the crew search desperately to find their lost at sea Captain and his comrade, hoping to do so before their enemies beat them to it.

With Chandler and Tex caught in a dangerous situation, Slattery has to step into the role as commanding officer. Torn between a mission with the fate of the world at stake and a Captain (and friend) in danger, Slattery has to find a way to get his people back without losing the most important asset: the vaccine prototype.

Rachel and Chandler ask for six volunteers to participate in human trials of her vaccine, but the tests could be a living hell as the virus and the vaccine do battle inside their bodies. Meanwhile back in the States, Chandler’s wife and father are doing everything they can to keep their family alive.

Chandler and his crew finally returns home, where a former D.C. power player is fending off a dangerous warlord who threatens her hopes of restoring law and order in society. Now with a location and a means to finalize their mission, Chandler sets out to save his dying family, only to discover something absolutely terrifying about this brave new world.