We're introduced to a ship and its crew. Malcolm 'Mal' Reynolds, the captain, Wash the pilot, Kaylee the mechanic, Inara the companion, Zoë and Jayne. Together the four of them salvage goods from wrecks in space and take them aboard their ship, Serenity. Though Mal feels that they're not going to get enough money with their salvage operations anymore and so take on passengers at Persephone. A doctor called Simon Tam, Shepherd Book and another man. Simon brings aboard a mysteriously large package and has an air of suspicion around him. Turns out the suspicion was needed as the other man who also boarded the ship works for the government, he's a law man and wants to take Simon in. A brawl breaks out and Kaylee gets shot. The Alliance are bearing down on Serenity and Mal can either run and help Simon and turn him in. But with Kaylee's gunshot wound Mal decides to tell Wash to run. Once Kaylee's settled and Simon's done what he can for her Mal goes to see what was in the box Simon was carting around. he opens it against Simon's wishes and inside is a girl Simon's sister. Simon tells the crew and passengers that River, his sister, is more than a gifted child. She was at a government run school who were hurting her, doing experiments on her, so he took her away and now the Alliance want them. They're outlaws. Mal agrees to have Simon on Serenity, after all a ship needs a medic.

The nine strong crew do what they can to keep flying. However the Alliance are never far behind looking for River and Simon. Mal takes whatever jobs he can to keep Serenity flying, but it often gets a bit tight and more than hairy. They go to a planet where Jayne's a bonafide folk hero. The ship nearly dies, with only the captain onboard to save her. Mal gets married, without his knowledge, though it turns out the woman's a manipulative girl with her own agenda. Wash and Mal get kidnapped and tortured by a man called Niska. But are rescued by the crew. The crew help Simon to find out what the government did to River by getting Simon and River into a hospital on Ariel. But the bounty on their heads was too much for Jayne, who brings them into the law. After they're all rescued by Mal and Zoë, Mal sense Jayne's betrayal and sets him straight. Simon finds out that River's brain has been played with, cut into on to many occasions and one pieces has been removed. The part of the brain that suppresses worried, anxious thoughts. River feels them all. During one mission, on behalf of Inara, the crew help out a "whore house". In the process Mal sleeps with Nandie, the owner of the house, which hurts Inara. Enough to make her want to leave Serenity. The short lived season ends with Serenity being boarded by a bounty hunter looking for River & Simon. But he's outwitted by River and booted off the ship.