- Joe Flanigan as John Sheppard (seasons 1–5 main) – a United States Air Force Major recruited to the Atlantis Expedition due to his intuitive mastery over Ancient technology. He becomes the de facto commander of Atlantis’ military contingent after the original mission commander Colonel Marshall Sumner is killed. His position is made official in season 2 after Atlantis re-establishes contact with Earth, and he is promoted to Lieutenant Colonel.
- David Hewlett as Rodney McKay (seasons 1–5 main) – a brilliant scientist who is a member of Sheppard’s team and the head of the Science and Research Departments on Atlantis. One of the foremost experts on Ancient technology, he was first introduced as a professional rival of Samantha Carter in the fifth season of Stargate SG-1.
- Rachel Luttrell as Teyla Emmagan (seasons 1–5 main) – the leader of the Athosians, a race of humans native to the Pegasus galaxy. She befriends Sheppard when he visits her homeworld and joins his team in order to fight the Wraith. She has the ability to sense the presence of the Wraith.
- Rainbow Sun Francks as Aiden Ford (season 1 main, seasons 2, 5 recurring) – a young First Lieutenant in the US Marine Corps, who is a member of Sheppard’s team in season 1. In season 2, he becomes mentally unstable due to an overdose of Wraith feeding enzyme, and abandons Atlantis.
- Torri Higginson as Elizabeth Weir (seasons 1–3 main, seasons 4–5 recurring) – a diplomat and expert in international politics, who leads the initial Atlantis Expedition after briefly serving as the head of Stargate Command in Stargate SG-1. She is a main character in seasons 1-3; in the season 3 finale she is critically wounded by a Replicator attack. She is a recurring character in season 4, having been captured by the Replicators.
- Paul McGillion as Carson Beckett (seasons 2–3 main, seasons 1, 4–5 recurring) – the Chief of Medicine of Atlantis in seasons 1-3. In the season 3 episode “Sunday”, he is killed in an explosion caused by Ancient technology. However, a clone of him created by the rogue Wraith “Michael” appears as a recurring character in seasons 4 and 5.
- Jason Momoa as Ronon Dex (seasons 2–5 main) – a weapons specialist from the Pegasus planet Sateda. After his world fell to the Wraith, he was turned into a “runner” and hunted relentlessly for seven years. He joins Sheppard’s team on Atlantis after Dr. Beckett removes his Wraith tracking device.
- Amanda Tapping as Samantha Carter (season 4 main, seasons 1–3, 5 recurring) – an astrophysicist and United States Air Force Lieutenant Colonel, who was a main character for the entire run of Stargate SG-1. In season 4, she is promoted to Colonel and given command of the Atlantis Expedition.
- Jewel Staite as Jennifer Keller (season 5 main, seasons 3–4 recurring) – the Chief of Medicine on Atlantis, who replaces Dr. Beckett in the third season finale. She is listed as a recurring character in season 4 and appears in the main title credits in season 5.
- Robert Picardo as Richard Woolsey (season 5 main, seasons 3–4 recurring) – a representative of the International Oversight Advisory, who first appeared as an agent of the NID in season 7 of Stargate SG-1. In season 5, he replaces Samantha Carter as commander of Atlantis.
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