Samuel Anders is a Cylon that was first encountered on Caprica as the leader of a group of civilians resisting the Cylon occupation of the planet. His resistance group included former members of the Caprica Buccaneers Pyramid team, of which Anders was the captain, as well as hikers and survivalists. Stranded pilots Kara "Starbuck" Thrace and Karl "Helo" Agathon run into the resistance and join forces after a tense stand-off. Thrace and Anders enter into a romantic relationship before Thrace and Agathon leave the planet in a Heavy Raider obtained by the Cylon Sharon, and Thrace vows to return for the survivors. Anders is later trapped in a collapsed building with D'Anna Biers, Caprica-Six], and Sharon Valerii, narrowly escaping death at Biers' hands due to the intervention of Caprica-Six. This event leads Six and Valerii to speak out against the war of extermination being waged by the Cylons against humanity, a movement which will lead to the Cylon occupation of New Caprica.
After Thrace is finally able to make good on her promise, she and Anders settle down on the newly discovered planet New Caprica and are married. A year after the discovery of the planet, the Cylons appear and set up a brutal occupation. Anders is one of the leaders in the resistance against the Cylon Occupation Authority, while the whereabouts of his wife, who is being held in a pseudo-marriage scenario by Leoben Conoy, remain a mystery. After rescuing Thrace during the exodus from New Caprica, Anders joins the Circle, a group set up by President Tom Zarek to secretly prosecute and execute people who collaborated with the Cylon occupation, but eventually leaves the group out of disgust with their methods. Anders and Thrace remain estranged due to the psychological effects of her imprisonment.
Following Thrace's apparent death, Anders joins the Colonial fleet as a rookie Viper pilot, with the callsign "Longshot" and the rank of ensign. He engages in a sexual relationship with presidential aide Tory Foster. It soon becomes apparent that both of them, as well as Colonel Saul Tigh and Chief Galen Tyrol, are hearing snatches of a strange song. As the fleet arrives in the Ionian Nebula, the four of them are drawn to the same empty room on Galactica and awaken to the fact that they are Cylons. Unsure what to make of this revelation, they nevertheless resolve to keep doing their jobs as part of the fleet. Anders joins the other Viper pilots in the Battle of the Ionian Nebula against the Cylon fleet, and is scanned by a Cylon Raider who positively identifies him as one of their own. This causes the end of the battle due to the withdrawal of the Cylon fleet, and plants the seed of the Cylon Civil War.
Anders is overjoyed by his wife's mysterious resurrection and assures her that he would still love her even if she turned out to be a Cylon. He is one of several crew assigned to the Demetrius under Thrace's command as part of a mission to find Earth, and backs up Thrace during an attempted mutiny on the part of the other crew by shooting Felix Gaeta in the leg. This injury later leads to the amputation of Gaeta's leg. Anders is a member of the party from Demetrius that forges an alliance with Natalie's rebel Cylon faction of Twos, Sixes, and Eights. He returns to Galactica', and does not take part in the Battle of the Resurrection Hub. Following the battle and the resurrection of D'Anna Biers, who alone knows the identities of all the Cylon Final Five, Anders does not attempt to join the rebel Cylons on their Basestar despite Biers' invitation. He and Tyrol tell Thrace to take a closer look at her Viper, which is receiving a signal audible to the four Final Five Cylons in the fleet. Tigh outs himself, Anders, and Tyrol to the Colonials, and the three of them are used as hostages by Acting President Lee Adama in an attempt to obtain the safe release of Biers' human hostages. The discovery of the signal from Earth in Thrace's Viper ends this stand-off, and the humans and rebel Cylons decided to proceed to Earth together. Acting President Adama grants the Cylons in the fleet an amnesty.
On the devastated ruins of Earth, Anders begins to recall memories of his past life as a member of the Thirteenth Tribe Cylon civilization 2,000 years ago. He was a musician, and he composed the music, which he played for his friends and a woman he loved. Anders was killed along with the rest of the populace during a nuclear attack, but he and the other four members of the Final Five were reborn by some pre-arranged mechanism.