An androgynous alien species called the Taelons arrive on earth, claiming to be companions of humanity, putting an end to crime, illness, and famine. Some are suspicious of the Taleons, and form a resistance movement. The resistance soon learned that the force that sustains the Taelons are breaking down, and they are using humans as test subjects in experiments to help save their species. The initial focus of the show was Commander William Boone and his partner, Captain Lili Marquette, who worked for both the Taelons and the resistance. After Boone was killed, the show introduced a new protagonist, Major Liam Kincaid, and began to play on the strengths of it's ensemble cast.
After Police Captain William Boone's wife is killed, he is recruited to work for the taelons, a seemingly benevolent alien race that has been on Earth for 3 years. To do so he will be implanted with a CVI- a cyber viral implant that will expand his mental abilities and allow him to control a bio-weapon of unlimited power. However before he can make his decision he is also recruited by the resistance, a group of humans who oppose the taelons being on Earth. Lead by Jonathan Doors, the resistance informs Boone that the taelons are not what they appear to be. The CVI implant brainwashes its subjects into following the taelon blindly, in effect controlling them. The resistance informs Boone that they can remove this aspect from the CVI on the condition that he works for both the taelons and the resistance. Boone accepts and now searches for the truth of why the taelons are on earth and if they are responsible for the death of his wife.
Boone attempts to track his wife's murderer. He is determined to find out if it was the taelon companion Da'an who ordered her death to get Boone to work for the companions or if it was the resistance that killed her, securing Boone as the resistance's eyes and ears of the companions.
Boone encounters Julie, a suicidal young woman with artificial limbs as hands, who is being used by a religious leader as a miracle when her hands are regenerated by taelon technology.
Boone investigates a serial killer programmed with a CVI who tried to kill Da'an when he enacted an ancient taelon myth of good conquering evil.
Boone is caught in the middle of his double life when his old flame comes back in his life claiming to be working against the companions.
Boone and Lili investigate a small Amish town after several of its citizens mysteriously die.
Oblivious to Boone and the resistance, Jonathan Doors comes out of hiding and launches a media campaign against the taelons, leaving Boone to clean up the mess.
When Lili's shuttle is stolen by a friend whose mission to Mars was cancelled, Boone, without breaking orders to find the shuttle for the taelons, has to help the resistance make the most of the stolen shuttle.
The "Skrills" have been bio-engineered on the Earth to be a weapon for the humans who assist the Companions. A "skrill" from the first generation infests a bio-engineer who goes underground, bent on freeing all "skrills" from the oppression of the Companions.
Several soldiers who have volunteered to train in Taelon Interdimensional flight have instead been the victims of strange experiments - some have disappeared all together. A high ranking officer kidnaps Da'an in an attempt to have his men released.
At resistance headquarters, Boone meets two molecular biologists, Sahjit Jinnah and his fiancee Rayna Armitraj, who are studying the alien probe captured after it wreaked havoc in an Amish community. A power surge causes Rayna to cut off the top of the probe, which responds by dematerializing her. Unaware of the situation, Sahjit and Boone discuss with Doors and Auger the probe's purpose, recalling its ability to replicate butterflies into killers. Launching the resistance into battle with the probe that may be studying Earth.
Sandoval's CVI is degenerating. While Dr Belman works to restore his CVI and save his life, Sandoval, free from his CVI, escapes to reunite with his wife, only to put her life in danger. Boone learns that Sandoval's CVI contained information about the Taelon's mission on earth, and tries to save Sandoval's life.
A construction blast unearths a grave marker belonging to a Taelon scout sent to size up earth for Companion occupation thousands of years ago. Boone must find the grave which contains the research, before Sandoval finds the grave. Da'an loses his position as the United Nations Companion to Zu'or, but keeps the American Companionship.
When a taelon experiment to create an new hybrid warrior goes wrong, an ancient alien evil is unleashed upon the Earth.
At a Conference of Psychic Sciences, "The Commonality" the Taelon psychic link has been invaded and the secret plans for Earth are known. Katya Petrenko possesses incredible psychic gifts and an interest in Boone. She confronts Zu'or, telling him that the Taelons must change their approach to humans, or they will destroy both races. Katya reveals that a taelon named Ma'el gave some humans the gift to break into "The Commonality". As Katya dies, Dr. Belman performs a brain transfer of all of Katya's knowledge to Boone.
Lili loads Augur's computer virus into the Taelon system and it takes affect immediately. System after system crashes and Lili and Da'an are in grave danger as the virus infiltrates the shuttle's computer and lurches them out of control. Augur thinks he can stop the virus, but he must send Boone deep into the building to access the central computer.
Colonel Purcell and agent Carter discuss if the body of Thomas Blanchard, a thief who was beaten brain dead, is suitable for them. Doors International head, Anne Portnoy, demonstrates a new Taelon device, an EMP (ElectroMagnetic Pulse) weapon. Boone meets with Doors and Augur to warn them of the EMP. They plot to steal the weapon to prevent the Taelons from using it against Earth. Before they can obtain the EMP, Blanchard steals it. Lili sneaks into Blanchard's hideout, but is discovered and taken hostage. Blanchard reveals to Lili that he is really her father, Colonel Purcell.
Major McIntyre confronted Rho-ha in Johnson's hospital room, a struggle ensued and McIntyre was killed. Boone and Sandoval defend Rho-ha, who is ordered to stand trial facing the death penalty for murder. The prosecuting attorney is Joshua Doors, the estranged son of Jonathan Doors. Travis Perkins, delusional Taelon supporter, has vowed to kill those who pose a threat to Rho-ha. Joshua confronts Rho-ha on the stand about the DNA experiments, Rho-ha becomes enraged and threatens to kill Joshua. Perkins is angry at the treatment of the Taelon and attempts a suicide bombing.
The Taelons introduce interdimensional travel to human customers. A young deaf-mute boy and his mother become separated during their travels through the portal. The boy appears and is now able to speak and hear. The boy is examined by Dr. Park, a resistance doctor, who discovers that he has been implanted with a device to restore his missing senses. Boone suspects that the Taelons are using the portal to perform experiments on humans. Doors sends Sahjit through the portal with a tracking device.
Ne'eg dies from being exposed to a devastating virus that was unleashed from an alien probe. The virus falls into the hands of a group of white supremacists, they release the virus into the Lincoln Hills homeless shelter. The deadly virus quickly spreads, threatening to decimate both the human and Taelon races. Boone, infected with the virus, comes up with an idea to develop anti-bodies against the virus but it may not be in time to prevent the virus spreading over earth.
A holographic image of Rayna, who was consumed by an alien probe, tells Augur that the Taelons are dismantling the probe which will kill her, and they will learn about the Resistance's secrets. Hearing of Rayna's appearance, Sahjit is determined to bring her back. The Taelon lab is under intense security and Augur hires a special operative, Michael Sloane, to lead the resistance team to infiltrate the Taelon compound to destroy the alien probe.
Divers stumble across a strange radiant canister while searching for sunken treasure. Upon opening the canister an alien being known as Ha'gel is released from its prison and assumes the identity of one of the crew and destroys the others. Boone is called to the crime scene and his suspicions are raised when he finds Taelon writing on the empty canister. Upon questioning, the Taelons tell Boone that Ha'gel is the last of an alien criminal caste. Afraid that Earth will learn the truth, the Companion's recruit the help of Beckett to deal with Ha'gel. Ha'gel assumes Sandoval's form, and confronts Beckett.