The struggle to respond to their destiny wears on the aliens' nerves. Max is now relied on to be the leader, but Michael's patience with Max is stretched to the breaking point. Everyone is concerned about the threat posed by hostile alien enemies that may have been alerted to their presence because they activated the communicators. Shreds of peeled skin which disintegrate when touched alert Nasedo to the presence of enemies in Roswell.

As fall begins, Liz keeps her distance from Max and takes a job as a student intern with U.S. Congresswoman Katherine Whiteaker. Whiteaker has carried out a public campaign to uncover the work of Agent Pierce and the FBI Special Unit. Nasedo, transformed into Pierce's form, uses Whiteaker to bring about the end of the special unit. But the discovery of radioactive bones in the desert, which Valenti knows are those of the real Pierce, peaks Whiteaker's curiosity.

An over-zealous deputy ties Michael to the skeleton as the prime murder suspect, and Valenti is forced to arrest him. Whiteaker suspects the skeleton contains isotopes of a non-earthly origin. Max breaks into a research facility and artificially ages the bones before scientists can test them for isotopes which are the by-product of Michael's attack on Pierce. The murder charges against Michael are dropped since the bones appear to be decades old. But their troubles are only beginning when Nasedo, coming to Max after being visciously attacked, implicates "The Skins" and dies in Max's arms.

Nasedo's death leaves Tess alone and without the protector she's known all her life. When her house is broken into and Skin shreds are found there, she moves in with Jim and Kyle Valenti. Tess's presence in his life is a test for Kyle's newfound adherence to Buddhist philosophy, but one that is easily reconciled, given Tess's sexy appeal.

Every stranger the gang encounters becomes suspect, especially Courtney, the new waitress at the Crashdown Cafe, and Brody Davis, the new owner of the Crash Museum. Max discovers that Brody's interest in Roswell stems from his belief that he was an alien abductee. As a wealthy computer mogul, he has the resources to pursue the scientific evidence that points to alien activity in Roswell on the day the communicators were activated. Max seems satisfied that Brody is no threat to them, but the gang is unaware that Courtney's skin is peeling off in sheets.

On the night of Isabel's 18th birthday, Isabel receives repeated visions of Tess, beaten, injured and in danger. Isabel tracks Tess to an abandoned factory where she was overpowered by the superior alien power of Congresswoman Whiteaker. Whiteaker reaveals to Isabel that the Skins have only 50 years to live because they lack human DNA. On their home world, Isabel was called Vilandra and betrayed Max to the Skins for the sake of her Skins lover. In order to save herself and Tess, Isabel must match her powers against Whiteaker's, finally destroying her. In her grief, Isabel returns to the Pod Chamber for some soul searching and discovers an alien power generator deep inside the cave, something refered to by Whiteaker earlier as the Granilith.

Michael wavers between suspscion of Courtney and attraction to her relentless flirting, which fuels Maria's jealousy. During a reunion in Roswell of the 509th Bomb Group, he meets Captain Hal Carver, a witness to the aftermath of the crash and the cover-up. Michael learns from him that there were 8 pods total, meaning there are four other alien hybrids on earth. Realizing that Hal may have saved his life 50 years before, Michael's heart softens toward Maria and the other humans who have helped him survive. But continued advances by Courtney, and Michael's responses to her, work on Maria's insecurities.

Max grows more frustrated by Liz's forced separation from him. Liz pushes him away with serious finality after Max from 14 years in the future comes back to tell Liz of the dire consequences to the planet if she doesn't find a way to get teen Max to fall out of love with her. After seeing Liz in bed with Kyle, the ploy Liz uses to convince Max it's over, future Max disappears, signifying the change in the timeline, while Max struggles with his confusion and anger over her rejection of him.

A covert Skins organization called "The Universal Friendship League" covers up Whiteaker's death. In a letter to Whiteaker, the League refers to "the Vilandra Project" which only has meaning for Isabel, who kept her knowledge of Vilandra and her betrayal a secret to the others. Traveling to Copper Summit, Arizona, the League's headquarters and Whiteaker's supposed home town, they come face to face with the enclave of Skins and learn about their plan to harvest new bodies being preapared in incubation tanks. The Skins masquerade as Whiteaker's family and friends. Their leader is Nicolas, posing as Whiteaker's younger brother.

Courtney confesses to Michael and Maria that she is a renegade skin, part of a faction who believed that if Michael had been ruler of their planet instead of Max, the planet would have entered a golden age. Together, they hurry to meet with the others in Arizona, arriving in time to destroy the incubation tanks and any chance the Skins had of replacing their dying "husk" coverings with earth-friendly bodies.

In a final bid for revenge, the Skins cause the human population to disappear from Roswell in order to reveal the whereabouts of the aliens. Valenti and Kyle, Liz and Maria are unaffected when they come back into town after the fact. Courtney self-destructs so that Nicolas won't be able to get information from her. One by one, the humans disappear, but Maria successfully breaks the Skins time-warping field affecting Roswell. Captured by Nicolas and subject to his tremendous power, only Tess defeats the Skins in a fiery rage. The Skins disappear in a flurry of snowy flakes.