The movie opens with a vignette talking about UFO's and conspiracies. It then opens to a scene where a group of government agents track a flying object that flies into Earth's atmosphere over Las Vegas. Henry Burke (Ciaran Hinds) gives the orders for his fellow agents to follow where it crashed and get whatever information they can.
Meanwhile, in town, cab driver Jack Bruno (Dwayne Johnson) picks up a couple of dudes in Storm trooper outfits, who speak in robotic voices to take them to the UFO Convention at Planet Hollywood. He takes their plastic rifles and points to a sign in his cab that says "NO WEAPONS".
Meanwhile, back in the desert, Burke and his men examine footprints, while something unseen rustles in the bushes, watching them. Through further analysis from his right hand man Matheson (Tom Everett Scott), they've taken humanoid form. Burke slowly backtracks how the two managed to get out of the desert overnight (the analysis is done when they get back to the office) and discover the two of them, disguised as teens, snuck onto a senior citizen's tour, headed right into Vegas.
Jack gives a ride to Dr. Alex Friedman (Carla Gugino), who's in town for the UFO Convention as a theorist investigating life on other planets. She can tell that Jack doesn't really believe in them from his description of the "nut jobs", but gives him a pamphlet anyway in case he changes his mind. That night, he goes back to his hotel, but can't sleep because of all the noise coming from the room next door. To pass the time, he beats up a punching bag.
The next morning, he heads to his cab to prepare for work, but two thugs pull up in a truck. It turns out they work for a local crime boss, and he wants Jack to come back to work for him. Jack explains he's out, but the thugs get in close, trying to say he's not. He slams them down on the hood. When a cop comes threatening to give them a ticket for their parking job, they leave, promising Jack that it isn't over.
Jack gets back into his cab and suddenly discovers Sara (AnnaSophia Robb) and Seth (Alexander Ludwig), the teens, in his back seat. They explain that they're in a hurry to get out of there, and show a huge wad of cash to Jack. He accepts the job, but gets slightly irritated by Seth's details in where they're going, since he's giving coordinates. He prefers Sara's simple approach of "that way".
After accessing cameras throughout the city, Burke discovers that the kids hopped into Jack's cabs, and orders cars to give pursuit.
The cab is now driving through the desert, where Jack is analyzing the situation with the kids. He thinks they're runaways. However, Sara interrupts when she notes that three trucks are in hot pursuit. Jack thinks they're just passing, but uses his evasive driving skills when they try to box him in. Jack thinks they're with the crime boss the thugs came from earlier and attempts to outrun them. They try to box him in again, but he escapes, leading to two trucks veering off the road. A third is still in pursuit. Seth gives his sister Sara a certain look, and she says, "don't". He disappears through the seat and stands on the road, and the truck, not seeing his sudden appearance, crashes right into him. It cracks into pieces and lands on the road, and Seth doesn't have a scratch on him.
Sara uses forceful powers to reverse gears on the cab and hit the accelerator pedal to back it up. The agents think they're going to ram them, but it stops just shy of doing so. Seth gets back in the cab without opening the door, unbeknownst to Jack. Still, he gets out, crowbar in hand, saying he's going to end this. He tells the agents, including Burke, that he said he is out and he means it. Burke assures him he has no idea what he's getting into. A flustered Jack gets back into the cab and drives away.
Hours later, he gets the kids to a cabin in the middle of nowhere. They give him the cash and leave, going into the cabin. He looks at the cash and realizes they overpaid him (with money stolen from an ATM, again, not known to Jack). He gets out and slowly enters the house to catch up with them, and they're crouched down, using some kind of sensor to find something. Seth locates it and activates a switch on a fridge, and it opens a secret panel. The kids go inside, and Jack follows, not knowing that a weird dude in a space suit is watching behind him.
They go into an inner area that looks like an atrium. Seth finds some egg-shaped thing and sets down another switch. He reaches inside and pulls out a sensor of some kind, and him and Sara are both excited. However, their excitement is short lived when the space suit guy charges after them with a laser cannon. Jack tries to hold him off, but gets knocked down. Soon, everything in the atrium is set ablaze, and Seth is knocked unconscious. Jack bewilders the space guy and gets the kids out of there as everything is blowing up around them. He gets in the cab and drives off with them in tow.
He stops and asks what the heck just happened out there. The space suit guy is in hot pursuit in his spaceship, shooting at them with everything he's got. Jack drives into a train tunnel and narrowly avoids the hunter's sensors, and the trio thinks they're safe. Seth insists that he shouldn't tell Sara the truth, as humans are untrustworthy. Sara disagrees. Jack starts to drive over a bridge, and the hunter reappears, shooting at them with lasers. They enter another tunnel, and Jack discovers that a train is coming from the other way, with the spaceship in hot pursuit. Sara makes the taxicab go faster, and it manages to escape a collision while the spaceship is totaled.
Back at the lab, Burke and the others know about the explosion surrounding the cabin and want it checked out. He also knows about the train collision and the possibility that someone else is in pursuit of the kids. No matter -- he wants the kids first.
Jack pulls over the cab and the kids spill the beans. They are in fact aliens, sent to Earth to retrieve something. He doesn't believe them, insisting that aliens are like little green men. To convince him, Sara levitates several objects in the cab. It freaks Jack out a little, and he agrees to help, driving the cab off. It's in bad shape after the multiple encounters it's been through. Meanwhile, we discover that the space guy survives the impact from his ship, and is slowly repairing his suit...
The cab makes its way into the small town of Stony Creek. Jack asks a local mechanic (Cheech Marin) to fix it, but he says he's closed. Sara uses her mind reading ability to slowly convince him, and Jack offers cash as well. While he's doing repairs, the trio head to a local restaurant to cool off. Sara is worried that Jack is going to ditch them, as she has telepathy powers and can read his mind. Seth is still annoyed by the fact he can't trust humans.
Thanks to the LoJack tracking on the cab, Burke and his men catch up to Jack. They surround the restaurant that the three of them are in, and he calls him to give him an ultimatum. Instead of turning them in, however, Jack gets the attention of a local sheriff and his men, saying that armed men are about to come into the restaurant. He slowly gets the kids to cover near the back, as the government men and the sheriff's team draw guns on each other. A local waitress, who helped clean the kids up earlier, lead them to a shaft where they can get out through the roof. Jack thanks her, while the government agent convinces the sheriff that he's with higher authority. They put their guns away.
Jack can't open the shaft door, as it's locked from the outside. Seth reaches up, slipping his hand through the metal and unsnapping the hinge from the outside. It opens right up, and Sara explains that Seth can molecularly manipulate items. They go across the roof as the agents close in on them and land in a neighbor's yard, where an angry dog confronts Jack. He thinks he's going to get attacked, but instead, it licks Sara in the face and shows compassion to her. She understands it.
They get into the cab (after paying the mechanic) and drive off. The agents try to give pursuit, but Sara uses her powers to electrically blow the engines on their cars as they pass. Burke tries to get a shot off, but the dog bites him in the arm and runs away. As the cab's about to leave, Sara makes it stop, and the dog climbs in. It then speeds away into the night.
The cab stops later on, after Jack has a discussion with the dog (through Sara), as it needs to go to the bathroom. He's not sure what to do now; since he's unable to help the kids find what they're looking for. However, Sara's mind reading brings up the name of Alex Friedman, the person Jack picked up earlier. So, they head back to Vegas.
They arrive at Planet Hollywood, where Jack has the valet park his cab. Meanwhile, one of the thugs he ran into earlier is on the phone, saying Jack just showed up and it's a big mistake. The three of them catch up to Friedman, who just got humiliated with her technical space discussion being laughed at by sci-fi fans. They go into a Mars exhibit, where Jack tells her the whole story. She doesn't believe it until her laptop drops on the floor, and Sara saves a collision by lifting it with her powers and handing it back to her.
Seth then activates a special screening device, showing them the whole universe. Sara admires Alex for pointing out a "smudge" on her readings -- it's actually their ship. They explain what they're doing there. Their parents were trying to research Earth to find resources for their dying planet, and want to inhabit it peacefully. Other people think that forceful invasion is the answer, including the space man that's in pursuit of the kids. So they need to get back to their planet with the proof -- the substance taken from the egg in the cabin -- or the planet may be doomed. Alex thinks she can get help from a colleague, and they go to see him.
The colleague is Dr. Donald Harlan (Garry Marshall), and after a discussion with two of his right-hand men, they lead the group to his trailer. Harlan explains that the only place they could possibly store their space ship, which is of tremendous size, is in a hidden base called Witch Mountain. It's a heavily fortified base and a suicide mission, but Jack relents and says he's taking them. Harlan wishes them luck and gives them maps.
Alex goes up to get her stuff, as she insists on coming along with Jack and the kids since she wants to prove her theories. Sara detects that she likes Jack, and he feels the same. The kids run off for a sci-fi display, and Jack begins looking for them. However, the two thugs jump him and drag him away, with guns hidden to his back. He then sees the two Storm trooper guys he mocked earlier in the cab, grabs their toy guns, and beats up the thugs. He runs off, looking for the kids.
Meanwhile, a cheesy sci-fi show is going on, with B-movie actors on the stage. This fascinates the kids, even though they think they're being made fun of. What they aren't aware of, however, is that the bounty hunter is in the group, ready to blast them. Sara lowers a light fixture on the space dude, crashing him through a monitor. Just then, Burke's men show up after they tracked Jack's cab through his license plate. The three of them get away, and the bounty hunter creeps off as Burke's men remain in hot pursuit. Just when they think they have Jack and the kids surrounded by slot machines, Sara sets them off so they spew a whole lot of money. Crowds flock to gather it, and the three of them escape, along with Alex, coming back from her room.
The cab speeds off down the city streets, with Burke's men in hot pursuit. They stop and surround it, only to find Harlan behind the wheel with his two friends in the back. They've taken Harlan's SUV, and are headed up to Witch Mountain. As the kids sleep, Alex and Jack get to know each other. Alex has always been about science, while Jack wants nothing more than to buy a '68 Mustang, like the one featured in the movie Bullitt. She's never seen it.
They arrive at Witch Mountain, surveying the entrance, which is five miles away. They slowly make their way towards it, unaware that a security camera is tracking them. As they climb down a ridge, Sara and Seth are both taken down by tranquilizer darts. Burke and his men capture them. Jack tries to put up a fight, but is subdued by two guards. Burke explains that he could go back to jail if he resists, and that Alex's seeking the truth won't do her any good, since no one believes her anyway. Jack simply refuses to fight any further, and this shocks Alex.
As Jack and Alex ride in a Jeep with two soldiers, she still can't believe he's given up. She slaps him, and it distracts the two soldiers long enough for them to get thrown out. Alex takes control, and Jack wonders when she knew that he wasn't giving up on the kids. (It was a ruse.) She says he hasn't given up on them so far.
They make their way through a tunnel access system into the base, after just narrowly escaping getting incinerated. Meanwhile, Burke is about to run some tests on the kids, even though his associates aren't sure about their body structures. He insists the work get done. Jack and Alex make their way inside, but their presence is soon known with an internal alarm system. As the others (including Burke) go to look for them, they sneak into the lab, subduing the other scientists and slowly awakening the kids.
However, Jack and Alex aren't the only ones infiltrating the base. The bounty hunter is also there, shooting back at the soldiers and forcing them to fall back. Jack, Alex and the kids make their way around the base until they locate the ship. Alex makes the scientists leave (by explaining it's under Burke's orders), but they're stopped short of entering by Burke and his men. They inadvertently fire on them, but Seth's powers bounce off the bullets, and they manage to get on board. They activate a computer panel and get the ship's engine revving as the bounty hunter enters the lab. He shoots at the men and notices the ship leaving, but not until it runs right into him, head on. The ship flies through the corridors as Burke orders the base to be shut down. With the doors closing, the kids fly the ship at high-speed and.it escapes into the night!
However, a stuck-open air lock seems to be dragging the ship down. Jack says he'll take care of it if the kids can fly the ship. He goes back trying to fix the airlock, only to run into the bounty hunter guy. They have a huge fight, and Jack eventually knocks off his helmet, revealing the alien dude's ugly face. Seth goes to help Jack while Alex sits in the passenger seat, unsure how to drive the ship with Sara. The manual airlock door opens, revealing a glowing energy source at the bottom of it. The helmet falls in and is completely vaporized. The hunter and Jack continue to fight until Jack falls in, just narrowly landing on a ledge next to the energy source. The hunter comes down to finish him off, but Seth distracts him and almost makes him fall in. Jack grabs the hunter, only to pull him up, punch him in the face, and make him fall into the source. BLAM! Vaporized. The two climb out of the chamber and the ship flies straight on. Back in the lab, Burke receives a call from the higher-ups in Washington, with obviously not-good news.
It lands back by the SUV, where everyone says their goodbyes. Seth apologizes to Jack for not trusting humans. They also give them a transmitter, so they can find them wherever they go. Sara gives Jack a hug goodbye, asking him to take care of the dog (Junkyard) and that he's a good man. The kids take off as Jack and Sara watch. The ship flies away at lightspeed.
During the credits, it's revealed that Jack and Alex collaborated on a book, and is a huge success with the sci-fi crowd. They walk through happy autograph seekers and past Harlan and his crew (who were glad to be a part of the story). A cab is waiting for them, only to pull away and reveal a suave '68 Mustang. Jack, Alex and Junkyard climb inside, but before they drive off, Alex discovers the transmitter going off, meaning the kids are coming back. The car drives out of Las Vegas.
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