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.

A snafu with the communications stones lands Col. Young's consciousness in an unknown being, resulting in a standoff between the Destiny and an alien vessel and the abduction of Chloe.

An enemy from the Milky Way has boarded the Destiny and has taken hostages. Is it possible that they know how to get back or have they stranded themselves as well?

As Young and Camille attempt to resolve the hostage crisis with Kiva, Destiny suffers from power fluctuations and blackouts due to its proximity to a binary pulsar.

Everett and the crew continue their efforts to save Destiny while holding off the Lucian Alliance invaders.

The crew encounters a ship remarkably similar to Destiny, which may hold the key to their returning home.

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

An alien creature attacks an exploration team from Destiny, taking two crew members captive.

The Destiny needs to be refueled but every time they come out of FTL the drones seem to be waiting for them. It's not obvious how the drones know they're there but it doesn't matter a great deal since they only have one more try before running out of fuel completely. Eli suggests they go through a blue supergiant star, though the heat it creates might destroy the ship. They have little choice so Col. Young evacuates everyone to the only planet available with the exception of Eli and Rush. Lisa also stays behind to collect some of the medicinal herbs they've grown only to be trapped just as the Destiny goes through the star. On the planet, Young and the others find evidence of a destroyed civilization - and the drones.

Eli and Rush have found a way to identify the location of drone mother ships using the Destiny's long range sensors. The bad news is that the Drones seems to be awaiting them at every possible stop along Destiny's path. They find a temporary solution to neutralize the mother ships but realize that they cannot engage in a major battle every time they need to re-supply. Eli suggest that they use the stasis pods for the crew and jump to the next galaxy, a trip that will take three years. All goes well until they realize that one of the pods has been damaged and one person will have to stay behind in the hopes of fixing the unit in the short time available or die.