Jack Bruno is a cab driver in Las Vegas, who is picking up and dropping off passengers to the UFO convention at the Planet Hollywood Casino and Hotel. One of his passengers is Dr. Alex Friedman, a failed scientist who is giving speeches about legitimate scientific theories of UFOs and outer space.
The next day Jack is approached by two large men telling him that Wolff would like to see him. After fighting them, Jack drives off, later noticing two children, Sara and Seth sitting in the back seat of the cab. They tell him they need to go to a certain destination and are willing to pay all they have ($15,000) to get there. Along the way, there are chased & vehicularly assaulted by guys in big black SUV's, whom Jack assumes are Wolff's men...not so, grasshopper. With a combination of Jack's driving & (mostly) the kids' powers, they evade their pursuers, who intend to find out who & what Jack is. They lead him to a run down house in the middle of nowhere. Meanwhile, Major Henry Burke searching for information on the two aliens that landed some days earlier.
When they arrive at the house, the children tell Jack that they will be re-united with their relatives soon. Before leaving Jack hears a crash coming from the house. He is startled to find them hiding behind a couch. Though grateful for his concern, the children tell him they must continue their journey without him, as they can trust no one. Nevertheless, Bruno decides to follow them, which leads him to the basement of the house. There the kids are pursued and attacked by a strange creature as they retrieve an object in a plant. They manage to escape from this creature.
When leaving they are attacked by a "Siphon", a creature built to destroy a certain target, in this case the children. The Siphon pursues them until it causes a crash of his spaceship into a train, the creature survives, though wounded. The trio eventually find themselves in a small town, hiding. They explain to Bruno that they are aliens from an distant planet, who are sent to Earth by their parents because the government of their dying planet intends to attack and invade Earth so that their kind may live on there. They also explain that the object they obtained at the house contains the results of an experiment which their parents set up. The research from this experiment will save their planet without having to attack and invade Earth. However their planet's military prefer the idea of invading Earth and sent the Siphon assassin to stop them. They are next pursued by government agencies trying to retrieve the children for experiments.
When Sara asks who Dr. Friedman, Jack remembers she is a scientist speaking at the UFO convention. They find her, tell her the whole story & convince her to help them. She does this by enlisting the aid of Dr. Harlan pseudo-scientist/conspiracy nut. All proceed to the UFO convention.
When the Siphon arrives, it prepares to attack but Sara uses her powers to knock him through a wall. Chases ensue, & eventually the team of 4 are captured by Maj. Burke. Burke wants to terminate Sara & Seth, but one of his underlings objects, tho not strenuously enough to disobey orders. The two humans escape and come to rescue the kids. The Siphon causes a distraction by attacking the base. They manage to free the children and reach their ship. By running the Siphon over they can escape but the Siphon hangs on and gets on board. Bruno and Seth battle the Siphon in the lower sections of the ship, unmasking him in the fight. Finally, Bruno defeats the evil alien by knocking him out of the ship's airlock, which kills him. Nothing is mentioned about the fate of Henry Burke, though he was last seen disappointed and upset for his failure and was talking to his boss on the phone, with a possibly of getting fired. The kids drop Jack and Alex off and after a tearful goodbye, they head back to their ship, but give Bruno and Alex a device that will allow the kids to always find them. And Sara gives Jack the power to use his brain to the mind reading ability.
During the end credits, Bruno and Dr. Friedman (now a couple) are speaking at a UFO convention about their new successful book called "Race to Witch Mountain". The last scene shows them driving off in a car Bruno dreamed of getting honestly as he had mentioned to Friedman earliera Ford Mustang similar to that driven by Steve McQueen in ''Bullitt''. As they are about to leave, the device the kids gave Bruno before they left goes off, indicating that they may be returning.