After a shadowy figure gets hung and coroner's report claims that Lupin III has been executed. However only one man refuses to believe that he's dead which is Inspector Zenigata. Upon observing the resting place of Lupin, he encounters the theif who is alive and well. During a brief chase, Lupin manages to escape the Inspector by using a hang glider. Some time later, Lupin and Jigen sneak through a pyramid in the middle of Egypt where they found the Philospher's Stone. Once they found the stone they accidently triggered an alarm system which alerts the Egyptian police who are teamed up Zenigata. The two thieves flee from the pyramid by motorcycle along with the help of Goemon and made their escape by driving Lupin's car that's located beyond the pyramid. In France, Lupin meets up with Fujiko to give her the stone as a present only to discover that Fujiko steals the stone right from him leaving him stun in the process. The stone that Fujiko took was actually a fake with a tranmitter inside it so that way Lupin is able to hear who Fujiko is working for. The contractor soon idsocvered that the stone is fake and plans to sends out two of his henchmen to kill Lupin for making a mockery out of him.
After defeating the pursuing helicopter and over size truck, Lupin, Jigen, and Goemon soon find the car and their hideout destroyed by the mysterious contractor's henchmen. Jigen and Goemon place the blame on Lupin for trusting Fujiko so much that is lead to the sacrifice of their headquarters and their only needs of tranportation. Lupin eventually tells them that he'll keep Fujiko out of their affairs. But that statement didn't change the fact that they have no supllies, rations, or any vehicle to aid them on their travels. So they travel the desert to the direction of the ocean, while accidently setting off some booby traps placed by the men that are after them. They eventually found a house stocked with rations and water. Everything was fine, until a wounded Fujiko showed up for Lupin's help. Lupin who could never stay mad at her ends up alienating Jigen and Goemon who want nothing to do with the treacherous woman. Later that night, Fujiko drugs Lupin and they both end up being captured by Flinch, one of the henchmen that tried to killed Lupin earlier. After Jigen and Goemon witness what happened to Lupin, their only clue is a piece of paper that says Water on it. They both travel to Rome to find info on Lupin's whereabouts. Jigen is being pursued by a goverment Agent named Gordon. Only for the agent to end up being grabbed by Jigen quick reflexes who is now threatening the agent for why he's being stalked. Only to end up being surrounded by Navy seals who one of them has Goemon under arrest. The navy bring Jigen and Goemon to a sea docked navy ship, to be interviewed by Starky, an important government official from America. He plays a tape of an interrupted conversation between a mysterious voice, the President & the General Secratary. Starky then asked Jigen and Goemon on who the mysterious voice is. Jigen however only states that if they knew they wouldn't be where they are now and provides Gordon with the paper he found earlier which doesn't sum up who the person on the tape was. Starky decided that Jigen and Goemon know nothing and releases them on the sole purpose of finding the mysterious man on the tape. Jigen and Goemon immidately know what to find Lupin after it turns out that the piece of paper had invisible ink written on it when dosed with water which reveals the word: Caribean.
Meanwhile on a Caribean island, Lupin managed to escape his prison cell and then he explores the island only to discover it has various historical figures who are all long dead including Napolean and Hitler. Lupin finally comes face to face with the man in charge of the island, Howard Lockewood who refers to himself as Mamo. Mamo gives Lupin an opurtunity to have eternal life but Lupin is only interested in getting the Philosper's Stone back. He manages to find the stone after his encounter with Mamo and finds Fujiko on the island as well. They both get chased by a group of henchmen and then find themselves in Mamo's lair. There Mamo reveals to both Lupin and Fujiko that the island is populated with clones. After deeming Lupin unworthy for eternal life, he tries to kill Lupin by meanings of torture. Lupin is saved by Jigen who puts a bullet through Mamo's head. The group then tries to escape from the island only for Goemon to end up in a duel against Flinch. Goemon learns that his sword isn't able to penetrate Flinch's armor so he instead cuts up Flinch's head which leads Flinch dead in the water. Goemon's sword is detipped much to his sorrow that his sword wasn't able to cut someone's armor. As he and the rest of the gang escape from the island by boat, they are chased by Zenigata who choose the wrong boat to pursue them.
Zenigata now finds himself ashore on a beach where he is met with his Commissioner who reveals to him that he's no longer on Lupin's case due to circumstances that are beyond the I.C.P.O.'s control. He tries to encourage Zenigata that this is an opportunity to take a vacation and spend time with his family he rarely sees. Zenigata however resigns from Interpol and pursues Lupin by himself. Then he annouces to himself that Columbia is the place where he arrests Lupin. Meanwhile Lupin, Fujiko, & Jigen are hiding out at an inn excluding Goemon who wished to train harder alone. They are then thrust into a trippy vision made by Mamo who reveals to them on how he's been involved with every moment in human history making him a God. After the vision Jigen and Fujiko were baffled if that was real or just an illusion. Lupin however debunks the vision by putting out that the furniture has been moved recently and that they were drugged by the coffee they were drinking earlier prooving the whoel thing was just a parlor trick. Mamo shows up to congraguate Lupin on his deductions and reclaims Fujiko by floating away with her. Lupin however dare Mamo to prove he is a god and not an illusionist. Mamo respond by setting off a massive earthquake. This earthquake alerted Gordon and Starky who now know where Mamo is located.
Lupin soon figured out where the source of the earthquake came from and followed it believing that it's where Mamo is hiding out in. Jigen decided to not be involved with the fight fearing that it's not worth dying over. Despite Jigen's warning, Lupin ventured out to the secluded hideout. Upon exploring the hideout Lupin managed to sabotage the missiles that were meant to wipe out the world in order for Mamo and the reluctant Fujiko to have the whole planet for their own. The missiles instead exploded at the launching ports. The furious Mamo takes Fujiko wih him to a large rocket while Lupin pursues him only to be fended off by a series of lasers. Lupin was in a tight spot only to rememnber that he still has the tip of Goemon's sword in his pocket which is the answer to how he'll be able to defeat Mamo. Lupin faces Mamo again who believes Lupin admits to defeat and even reveals to Lupin that the Lupin who got executed was in fact a clone and the Lupin really is the legit Lupin. As another series of lasers shoot out Lupin uses the blade's tip to deflect the lasers towards Mamo who gets incarcinated from the blast of the beams. Lupin believed that he killed the real Mamo and not a clone, only for the rocket to emere and reeal a giant brain who proclaims to be the original Mamo. He plans to leave Earth by rocket and one day return to it as a God. Before the rocket left, Lupin placed an explosive device which denotinated in space. The gigantic brain is no longer protected in it's own glass case and drifts towards the sun where Mamo is finally no more. After escaping from the hideout, Lupin gets handcuffed by the ankles by Zenigata who handcuffs his own ankle making sure Lupin will not escape by foot. Lupin tried to make Zenigata think that the real Lupin was executed, but Zenigata didn't care if he was a clone or not. As long as there's a Lupin in the world, Zenigata stated he'll always be there to try to arrest that Lupin. Fujiko was about to offer Lupin some help until the entire hideout is bombarded by missiles being launched by the U.S. government lead by Gordon himself. Who is making sure that nothing will live after bombing the whole location with nukes. Jigen shows up by plane but only managed to save Fujiko leaving Lupin and Zenigata forced to dash through the stretched field that is being striked by missiles. Managing to evade any of them that was about to kill them.