While working in his basement, Quinn Mallory opens the gateway to parallel worlds. For a test run, Quinn invites co-worker Wade Welles and his teacher, Professor Arturo, along. Upon opening the vortex, Quinn uses too much power, which causes the vortex to suck them in along with Rembrandt "Crying Man" Brown, who happened to be driving by Quinn's house. The four arrive on a world that experienced an ecological disaster and will have to survive until the timer hits zero.
After barely escaping the last world, the Sliders think they are home. But to their horror, Quinn and Arturo learn they are not and have instead arrived on a world where the Soviet Union rules America. Rembrandt has been arrested for trying to use American money and the only way to save him is for the others to help a group of revolutionaries rescue their imprisoned leader.
On a world where being smart is the equivalent of being a sports star, Quinn is a popular college athlete and finds his double had underhanded dealings with gangsters. Meanwhile, Arturo discovers his late wife is alive on this world and tries for reconciliation after learning she is pressing for divorce.
After separating from Ryan and Henry the dog, the Sliders make a rough landing that reopens Quinn's bullet wound. On this world of mysticism and superstition, a witch doctor heals Quinn and has brains on the mind when they can't pay the bill. On the run from bounty hunters, the Sliders only hope is the mysterious Sorcerer, a man who could possibly get them home.
A lightning bolt strikes the vortex during a slide, damaging the timer and trapping Quinn on the astral plane. Now the Sliders are stranded on a world with 1950s technology and Quinn can not be seen by the others. He tries to get the help from the only one who can see or hear him, a girl that has a history of hearing voices.
On a world where everything west of the Mississippi is part of the Nation of Texas, corporate lawyers carry gunslinging ways of the Old West. After Quinn gets mixed up in a showdown, he gains the reputation for fastest draw in San Francisco and tries to prevent the hostile takeover of a family-owned computer company.
The Sliders land on a world where San Francisco is a national park dedicated to the preservation of dinosaurs, which is home to a deadly Allosaurus. A bad fall causes Arturo to injure himself and lose the timer. Quinn goes out alone to search for it, while the others hide out from the Allosaurus in a cave.
Wade literally meets the man of her dreams, Derek Bond, on a world where ten percent of the population possess psychic abilities. It turns out Derek is a psychic and is next in line for the powerful position of Prime Oracle. But the future gets grim fast as Rembrandt and Arturo become prime suspects in a murder that hasn't happened yet.
The Sliders land in the middle of a strange invasion and Quinn uses the timer to bring down one of the ships. Before barely escaping, the Sliders learn these new villains can slide at will and are soon captured on the next world. They learn their captors are the Kromaggs and are intent on conquering every parallel world.
The Sliders find themselves running into the same people on each new world, one of them being Quinn's former love, Daelin. After encounters on worlds where the Spanish rule America and Daelin is an abused wife, the Sliders arrive on a world where time moves backwards and they are accused of Daelin's murder. Quinn wants to save her, but it could have disastrous results.
On a world where people are enticed by consumerism and giant malls in the sky, the Sliders get jobs as mall employees to find the mother of an abandoned child. Arturo is a reluctant Santa, Rembrandt and Wade his elves while Quinn gets an administrative job. Meanwhile, Wade faces some strong emotions when she meets her sister and father.
Quinn and Maggie return to her world with Earth Prime's coordinates stored in Jensen's timer. As Wade makes the final list for those who can slide to safety, Arturo races to modify the new timer to slide more people. Unfortunately for them, an unexpected danger lurks the base and one Slider will not make it to the next world.
The Sliders track down Quinn's long lost brother, Colin, to a Amish-type Earth. Quinn convinces Colin they are brothers and to slide to find their true home. But on the next world, a double of Colin's former love takes advantage of him and involves him in a scam to steal cryogenically frozen bodies.
The Sliders arrive on a world where clones are harvested for spare body parts. Quinn's double is blinded in a lab accident and when Quinn tries to help, he is mistaken for a clone. Meanwhile, the others inadvertently rescue the clone, which Colin tries to teach the importance of family and sacrifice.
A rough slide separates Quinn and Maggie from Rembrandt and Colin for a brief time. Soon after they reunite, Quinn and Maggie become seriously ill and appear to be dying of old age. Unable to help them themselves, Rembrandt and Colin will have to rely on someone claiming to be Quinn and Maggie's son.
With nearly a month until their next slide, the Sliders find themselves extremely bored on a dull world. While the others get jobs, Rembrandt dives into a sci-fi book that bears more than a resemblance to their lives. When the Sliders track down the author, they learn he came from Quinn and Colin's home world.
The Sliders arrive on a small island, with a very sick Maggie in tow. While looking for help, Rembrandt, Mallory and Diana meet the monks of a secluded monastery. Reluctantly, the monks allow them to stay and give Maggie medical attention. But the Sliders soon learn the monks have a secret and won't allow them to leave.