In the year 2058, Earth will soon be uninhabitable after the irreversible effects of pollution. The United Global Space Force serves as the planetary government. Professor John Robinson (William Hurt
), lead scientist of the Jupiter Mission, will lead his family, wife Maureen Robinson (Mimi Rogers
), daughters Dr. Judy Robinson (Heather Graham
) and Penny (Lacey Chabert
) and son Will (Jack Johnson
) to the habitable planet Alpha Prime to prepare it for colonization by building a hypergate in orbit. The Jupiter 2 is equipped with a hyperdrive that allows faster-than-light travel, which will eventually be employed to evacuate the citizens of Earth. However hypergates must be constructed on Earth and Alpha Prime to provide stable points of departure and arrival. The project is accelerated after Global Sedition terrorist forces send two armed fighters to destroy the hypergate under construction and kill Jupiter 2's pilot, Captain Daniels. Major Don West (Matt LeBlanc
), a fighter pilot from the hypergate defense force, manages to destroy the enemy fighters, but his risky stunt in saving a fellow pilot gets him in trouble with his superiors. When he defends himself by putting his friend's life over that of his craft, John Robinson thinks he's the perfect man for the job. Major West is the new pilot of the Jupiter 2, despite his protests.
Dr. Zachary Smith (Gary Oldman
), the mission's medical expert, is bribed by the Global Sedition to sabotage the mission and reprogram the robot to destroy the Jupiter 2 and the Robinsons. Betrayed by his employers, he is left as an unwilling stowaway as the ship blasts off. The sabotage by the robot altered program causes the ship to veer towards the sun. Realizing that it would be impossible to escape the sun's pull at such close range, Major West and Professor Robinson decide to fly through the sun, using the ship's hyperdrive. Unfortunately, without a hypergate to warp to, the ship and its crew end up in a random (and apparently uncharted) part of the galaxy.
The crew discovers a "hole in space", which they presume is a hole to the future. Soon afterwards, they encounter the Proteus, an Earth ship from the future. The fact that it was a UGSF ship of unknown design piloted by Don's friend, who looked much older and been promoted to Major, seemed to confirm that theory. However, the ship had been infested with carnivorous and cannibalistic silicon-based spider-like lifeforms, one of which scratches Dr. Smith as they try to escape. They lose the robot, which Will had reprogrammed to follow his commands, and Major West overloads the Proteus' engines, destroying the ship and annihilating the spiders, over Professor Robinson's objections. The shock wave from the explosion damages the Jupiter 2, and they crash-land on a nearby planet.
John and Major West confront each other over what happened, but Maureen threatens to relieve both of them of command if they don't stop. On the mysterious planet, she locates a fuel source with which to refuel the damaged engines of the Jupiter 2. However, it lies in the center of a strange, growing bubble of mysterious origin. While the ladies repair the ship and Will tries to rebuild the robot, Professor Robinson and Major West explore the bubble and discover it is actually an area of time distortion where alternate future versions of Dr. Smith and Will (Jared Harris
) have constructed a time machine, powered by their Jupiter 2's power core. Will wants to use it to go back to the day they left Earth and stop the launch, since in his future his father left and never returned, and the women were killed by the spiders on the Proteus. The younger Will and Dr. Smith go after them, only Dr. Smith betrays Will and attempts to reprogram the future robot to take over the time machine. They are all betrayed by the future Smith, who is revealed to have transformed into a giant space spider/human hybrid as a result of the wound he received on the Proteus. He was the one to kill the women and kept Will alive long enough to build the time machine. He then reveals his plan to go back in time to Earth before the Jupiter 2 lifts off, destroy the ship, and conquer the planet to spread his spider race across the Earth. John tells Major West to take Will back to the ship and escape while Robinson battles Spider Smith. With the help of a dagger the younger Will made for him, John battles Spider Smith, wounding him and cutting open the egg sac with his young spiders in it. As the spiders eat their own wounded, they crawl out and consume Spider Smith, giving John the chance to send Spider Smith into the time machine's force field, killing him.
The family attempts to escape, but the time bubble has made the planet unstable, and it is violently breaking apart. In addition, without the core material the ship still does not have enough power to reach escape velocity. The stranded John Robinson watches as the Jupiter 2 is hit by debris and explodes in the sky. Future Will realizes his father does indeed love his family, choosing to save him rather than taking the core material from the time machine and escaping. Future Will reprograms the time machine and sends John through it, taking him back to the ship several hours before. Rather than attempt to escape into the atmosphere, John commands West to pilot the ship through the planet's core as it is breaking up, enabling them to use the planet's gravity to propel the ship through the other side. His idea works and they escape, but the collapsed planet forms a small black hole that begins to suck in the Jupiter 2. Once again the Robinsons must activate the hyperdrive to escape. They set course for Alpha Prime, having downloaded the detailed star charts from the Proteus, and launch themselves into hyperspace.