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.

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.

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.

Dr. Nicholas Rush and Chloe suffer nightmares following their ordeal on the alien vessel, and Rush suspects that a tracking device may have been placed on the ship's hull. Later, a splinter group on Destiny executes a coup with life-threatening consequences.

Now firmly in control again, Col. Young and the other military personnel try to find a way to live with the civilians who tried to take control of the ship. When the Destiny prematurely drops out of FTL due to a computer glitch, they find both a sun and an Earth-like planet that should not be there. Rush concludes that the entire system was created by an alien race that is far beyond their imaginations. With the ship malfunctioning and a month's worth of repairs before it can jump again, several of the military and civilians decide to spend time on the planet. Hard feelings from the mutiny persist and it's an opportunity for everyone to mend fences. When the time comes to return to the Destiny, several of them decide they want to stay on the planet. Young is prepared to let them stay, but he imposes severe conditions.

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.

Lt. Tamara Johansen tries to track down what is causing the crew to hallucinate.

Earth's Stargate Program isn't the only group in the Milky Way that's interested in the Ancients' Destiny. What's worse, this long-time foe may have a spy among those closest to the Icarus project.

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.

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.

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

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.

Rush and Young investigate an abandoned alien craft which is just outside the Destiny. While they do this, the crew onboard the ship find the bridge and discover that Rush is responsible for the countdown clock not activating when the ship emerges from FTL.

Members of the crew left behind in another galaxy make a shocking return to Destiny.

The crew's new-found control over Destiny's flight path introduces new risks when they find themselves in the middle of a war between two races.

Locked in a battle with a Drone Command Ship, the Destiny is surprised by the arrival of the Aliens that abducted Rush and Chloe.

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

Camille and Sgt. Greer are trapped when Homeworld Command comes under attack.

Destiny comes upon a colony where the people claim their civilization was founded two thousand years earlier ... by Destiny's crew.

While attempting to return a group of colonists to their home, the crew finds that the planet is on the verge of seismic destruction.

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.