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.

Severe rationing can't save the Destiny's dwindling water supply, forcing Colonel Young and Lieutenant Scott to seek out drinkable water on a deadly ice planet.

Visiting a newly discovered jungle planet, the crew is amazed to recover a Kino by the gate. Downloading the Kino data, Eli discovers video of the team, which appears to have been shot during an earlier visit. The mystery of the video’s origin becomes a secondary concern as members of the team start falling ill.

Aboard Destiny, Dr. Rush supervises the exploration of new areas of the ship. Looking for resources to make their everyday lives easier, the crew stumbles upon a piece of Ancient technology that carries the promise of a way home. While somewhat familiar with the find, Dr. Rush can’t guarantee the safety of using it, bringing him and Col. Young to a standoff on what to do.

Everyone is shocked when a member of the crew is found dead from a gunshot wound. While at first glance it appears to be suicide, the gun is nowhere to be found. The crew is confined to quarters while a search is performed and when the gun shows up in Col. Young’s quarters, he becomes the number one suspect.

The Destiny has jumped into hyperspace and is now traveling through an inter-galactic void. They've also been unable to locate Eli, Chloe and Scott who have been left behind. Dr. Rush has calculated that based on their current energy consumption, the Destiny has insufficient fuel to reach the next galaxy and they are doomed to die. The engines suddenly fail however and they arrange for an expert, Amanda Perry, to come on board via the communication stones and help them out. Perry and Rush have known each other for many years but as a quadriplegic, is experiencing what life has to offer. On Earth, Camile Wray's consciousness has been transferred to Perry's body and is wheelchair bound.

Desperate for food and water, Rush directs the ship to a planet that has been locked out of Destiny's controls. Young and Wray clash over what to do with the Alliance prisoners.

Chloe behaves in a bizarre way, prompting a search of her quarters, where Lt. Scott finds a journal penned in an alien language. Elsewhere, Eli copes with his mother's medical condition.

Young is plagued by mysterious dreams where Destiny is destroyed by alien attackers no matter what he does.