When Icarus Base is attacked, it's inhabitants are forced to flee through the Stargate. The base was created on a distant planet to take advantage of a powerful energy supply located there. Their goal is to try and determine the purpose of the mysterious ninth symbol of the Stargate which they have never been able to lock in. In going through the Stargate, they are transported not to Earth but onto an very old, apparently uninhabited but huge spacecraft. With the group's commander injured, Lt. Scott and the chief scientist, Dr. Nicholas Rush lead the exploration of the craft. Several areas of the ship have been damaged but it is basically functional. They are able to learn that they are in fact billions of light years from Earth.

The survivors arrive on an uninhabited ship floating billions of light years away from Earth. Panic spreads throughout the group and Col. Young, who was severely injured during the escape, transfers command to Lt. Matthew Scott, before lapsing into unconsciousness. Teams led by Dr. Rush and Sgt. Greer try to make sense of the situation, while Lt. Tamara Johansen, a medic who was days away from leaving the program, is thrust into the role of chief medical officer.

With the air supply failing on the Destiny, a team disembarks to a desert-like planet in search of the mineral needed to scrub the ship’s air of carbon dioxide. After testing numerous sand samples without success, and with their window of opportunity closing fast, the group opts to split into two to cover more ground, despite the unbearable heat.

The Destiny suffers a power crisis, putting the lives of the stranded crew in jeopardy and forcing them to consider abandoning the ship.

With the ship on a collision course, the crew must decide who will stay and who will flee on the shuttle to try and find a habitable planet.

With the situation onboard the Destiny dire, General O'Neill and Home World Command orders Col. Young to execute a high risk plan concocted by the I.O.A. scientists which, in theory, could return the crew to earth.

When Scott's team explores a new planet, a plant-like organism infects the lieutenant, causing him to hallucinate a life back on Earth where he is getting married.

Rush travels back in time to avert a disaster, meeting a past version of himself.